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76 publications mentioning mmu-mir-128-2

Open access articles that are associated with the species Mus musculus and mention the gene name mir-128-2. Click the [+] symbols to view sentences that include the gene name, or the word cloud on the right for a summary.

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[+] score: 438
Other miRNAs from this paper: mmu-mir-128-1, mmu-mir-24-1, mmu-mir-24-2
Accompanied with the upregulation of SUZ12 protein, downregulation of negative cell cycle regulators (such as p27) and upregulation of downstream positive cell cycle regulators such as Cyclin E and CDK2 were observed in the miR-128 -deficient heart. [score:12]
Analysis of i KO hearts at day 7 after TAM injection showed that the expression of miR-128 target SUZ12 was significantly increased, accompanied by downregulation of the p27 and upregulation of Cyclin E and CDK2 (Fig.   8b). [score:11]
To better define how the interaction between miR-128 and Suz12 might mediate cell proliferation in vivo, we first analyzed the expression of cell cycle-related genes in miR-128 [−/−] hearts at P7 and found that expression of SUZ12, cyclin E and cyclin -dependent Kinase 2 (CDK2) was elevated in miR-128 [−/−] P7 hearts compared with hearts from control mice (Ctrl) while the CDK inhibitor (CDKi) p27 was downregulated (Fig.   4g, h). [score:9]
Moreover, the analysis of genes downregulated in miR-128 [OE] showed statistically significant enrichment of genes downregulated after small interfering RNA (siRNA) inhibition of components of polycomb repressive complex 2 (PRC2), Suz12 in particular (Supplementary Fig.   7C). [score:9]
Overexpression of miR-128 significantly reduced the protein level of SUZ12, whereas inhibition of miR-128 led to its increased expression (Fig.   4d, e). [score:7]
Functional enrichment analysis of the genes that are both downregulated in miR-128 [OE] hearts and are predicted targets of miR-128 is performed using PANTHER enrichment analysis tool [57]. [score:6]
By comparing the downregulated mRNAs identified in miR-128 [OE] hearts relative to Ctrl hearts with all possible predicted candidate miR-128 target genes [19], we found 87 genes that contained the predicted binding site at the 3′UTR (Supplementary Fig.   7A). [score:6]
Among the target genes regulated by miR-128, is Suz12 whose expression is significantly lower in adult hearts. [score:6]
Having established a correlation between miR-128 overexpression and inhibition of CM proliferation, we asked whether loss of miR-128 is causal for CM proliferation. [score:5]
Deletion of miR-128 stimulates postnatal CM proliferationHaving established a correlation between miR-128 overexpression and inhibition of CM proliferation, we asked whether loss of miR-128 is causal for CM proliferation. [score:5]
Using a gain-of-function genetic approach in our neonatal cardiac injury mo del, we found that miR-128 overexpression inhibited CM proliferation and neonatal heart regeneration. [score:5]
Fig. 6Overexpression of miR-128 inhibits neonatal cardiac regeneration. [score:5]
Co-transfection of HEK293T cells with the Suz12 3′UTR plasmid (WT) and miR-128 mimic resulted in a significant decrease in luciferase activity compared with cells co -transfected with the negative control or the mutated 3′UTR target sequence (Mut), indicating that Suz12 is a direct target of miR-128, consistent with a previous report [22]. [score:5]
d, e Western blot analysis of SUZ12 expression in neonatal CMs treated with either vehicle (Ctrl), miR-128 mimic (miR-128) or miR-128 inhibitor (Anti- miR-128) (n = 3). [score:5]
In order to examine whether the postnatal upregulation of miR-128 occurs specifically in the CMs, we isolated CMs from P1 and P28 hearts, respectively, and found significantly higher expression of miR-128 in P28 CMs when compared with P1 CMs (Fig.   1f). [score:5]
As previously reported [15], miR-128 was predominantly expressed in brain tissue but was also expressed in the heart (Supplementary Fig.   1B). [score:5]
In summary, our study demonstrates that we can activate endogenous CM proliferation by targeting miR-128, and that this strategy is a potentially valuable approach for inducing myocardial regeneration, and may lead to major therapeutic advances in the treatment of human heart disease. [score:5]
Furthermore, cardiac-specific overexpression of miR-128 in early postnatal mice suppresses CM proliferation and causes impaired cardiac function. [score:5]
Overexpression of miR-128 inhibits cardiac regeneration. [score:5]
These findings suggest that inhibition of CM proliferation by miR-128 overexpression can impair cardiac regeneration in a neonatal mouse mo del. [score:5]
As a neuronal-enriched miRNA 15, 27, miR-128 is associated with central nervous system development 28, 29 and is downregulated in gliomas [30]. [score:5]
Downregulation of miR-128 accelerates glioma-initiating neural stem cell proliferation and contributes to the development of gliomas [31]. [score:5]
Although it was previously reported that miR-128 regulates apoptosis by targeting peroxisome proliferator-activated receptor gamma (Pparg) [24], we found no significant differences in either PPARγ expression or apoptosis in i KO hearts when compared to Ctrl hearts at day 7 after TAM injection (Supplementary Fig.   10C, D). [score:5]
b The expression level of miR-128 during heart development (n = 6) analyzed by qPCR, including embryonic day 10.5 (E10.5), E14.5, postnatal day 7 (P7), and P28. [score:4]
In vitro when miR-128 was knocked down using a specific miR-128 inhibitor (designated as Anti- miR-128) (Supplementary Fig.   4A), the neonatal CMs became dedifferentiated after 7 days. [score:4]
Hearts from miR-128 [fl/fl] (Control mice, Ctrl) and miR-128 [−/−] mice were harvested and analyzed at P7, at the time when most CMs have exited the cell cycle and become post-mitotic 6, 7. Downregulation of miR-128 in hearts from miR-128 [−/−] mice was confirmed by qPCR (Fig.   3a, b). [score:4]
NS designates not significantTo investigate whether miR-128 regulates Suz12 expression, mouse neonatal CMs were transfected with a negative control (Ctrl), a mimic of miR-128 (miR-128), or an inhibitor of miR-128 (Anti- miR-128) and assessed for the level of SUZ12 by western blot analysis. [score:4]
The correct insertion of the miR-128 cassette and successful removal of the neomycin cassette were confirmed by PCR analysis with the primers listed in Supplementary Table  1. Mice with doxycycline-inducible CM-specific overexpression of miR-128 (miR-128-3p) were generated by crossing α-MHC-tTA (The Jackson Laboratory) mice with miR-128 [TetRE] mice, in which tetracycline-responsive transcriptional activator (tTA) expression is under the control of α-MHC promoter. [score:4]
Generation of mice with conditional overexpression of miR-128A construct was engineered for knockin of the miR-128 (miR-128-3p) gene into the Rosa26 locus. [score:4]
In contrast to neonatal hearts, the protein levels of SUZ12 were lower in the adult heart (where the CM proliferation ability is quite limited) (Fig.   4b, c), paralleling the upregulation of miR-128. [score:4]
We demonstrate that (1) The upregulation of miR-128 in heart tissue is associated with the cell cycle exit of CMs during postnatal growth. [score:4]
NS designates not significant To investigate whether miR-128 regulates Suz12 expression, mouse neonatal CMs were transfected with a negative control (Ctrl), a mimic of miR-128 (miR-128), or an inhibitor of miR-128 (Anti- miR-128) and assessed for the level of SUZ12 by western blot analysis. [score:4]
Zhang Y MicroRNA-128 inhibits glioma cells proliferation by targeting transcription factor E2F3aJ. [score:4]
The correct insertion of the miR-128 cassette and successful removal of the neomycin cassette were confirmed by PCR analysis with the primers listed in Supplementary Table  1. Mice with doxycycline-inducible CM-specific overexpression of miR-128 (miR-128-3p) were generated by crossing α-MHC-tTA (The Jackson Laboratory) mice with miR-128 [TetRE] mice, in which tetracycline-responsive transcriptional activator (tTA) expression is under the control of α-MHC promoter. [score:4]
To further test whether miR-128 regulates Suz12 expression, we constructed a vector containing luciferase reporter with a DNA sequence encoding the complete 3′UTR from mouse Suz12 (designated as WT), and a mutated vector (designated as Mut) containing mismatches in the predicted miR-128 -binding site in the 3′UTR (Fig.   4f). [score:4]
A miR-128 [OE] mouse mo del in which miR-128 was overexpressed in a CM-specific and temporally controlled (by Dox withdrawal) manner (Fig.   6a) was used to test whether miR-128 regulates cardiac regenerative capacity in neonatal mice. [score:4]
Conversely, knockout of miR-128 reactivates CM proliferation and cardiac regeneration in the adult mice, in part through modulation of cell cycle-related genes by targeting Suz12 in the heart. [score:4]
By E10.5, miR-128 [−/−] hearts exhibited marked downregulation of miR-128. [score:4]
Zeng XC Li L Wen H Bi Q MicroRNA-128 inhibition attenuates myocardial ischemia/reperfusion injury -induced cardiomyocyte apoptosis by the targeted activation of peroxisome proliferator-activated receptor gammaMol. [score:4]
Interestingly, our RNA-seq data set revealed downregulation of Erbb2 (NRG1 co-receptor) in miR-128 [OE] heart. [score:4]
In vitro, direct inhibition of Suz12 by siRNA (si- Suz12) in cultured miR-128 [−/−] neonatal CMs reversed the pro-proliferative effect conferred by miR-128 deletion (miR-128 [−/−]), as evidenced by a significant decrease in the number of Ki67 [+] CMs in the si- Suz12 group in contrast to control group (si-Ctrl) (Fig.   5a–c). [score:4]
These data indicate that the downregulation of p27 induced by miR-128 deletion is attributed, at least in part, to PRC2 mediated gene silencing. [score:4]
To assess the potential therapeutic benefit of miR-128 inhibition in MI, we generated a cardiac-specific, tamoxifen-inducible miR-128 knockout mouse mo del. [score:4]
Interestingly, we found that miR-128 expression was significantly increased during heart development (Fig.   1e). [score:4]
Witman N Heigwer J Thaler B Lui WO Morrison JI miR-128 regulates non-myocyte hyperplasia, deposition of extracellular matrix and Islet1 expression during newt cardiac regenerationDev. [score:4]
Generation of mice with conditional overexpression of miR-128. [score:3]
Further analysis is underway to explore the association of miR-128 activation in pathogenesis of congenital heart disease involving abnormalities of myocardial growth. [score:3]
Control (Ctrl) mice were miR-128 [TetRE] mice, and miR-128 overexpressing mice (miR-128 [OE]) were α-MHC-tTA; miR-128 [TetRE] mice. [score:3]
Taken together, these data indicate that CM-specific overexpression of miR-128 induces early CM cell cycle exit, compensatory pathological growth of CM (hypertrophy), and impaired cardiac homeostasis. [score:3]
Right panel shows the qPCR analysis of miR-128 expression in Ctrl and miR-128 [OE] mice (n = 5). [score:3]
i qPCR analysis of miR-128 expression in Ctrl-tdTomato and i KO-tdTomato hearts (n = 5). [score:3]
After the cells were allowed to adhere for 24 h, miR-128 mimic (50 nM, Dharmacon, C-310957-01-0005), miR-128 inhibitor (50 nM, Dharmacon, IH-310957-02-0005), or siRNA against Suz12 (50 nM, Dharmacon, L-040180-00-0020) transfection were performed according to the manufacturer’s instructions. [score:3]
Moreover, the expression of miR-128 in CMs was significantly higher than in non-CMs (e. g., cardiac fibroblasts, CFs) (Fig.   1g). [score:3]
a Schematic showing the generation of mice that overexpress CM-specific miR-128 after doxycycline (Dox) withdrawal. [score:3]
g Comparison of miR-128 expression by qPCR in cardiac fibroblast (CF) and CMs (n = 5). [score:3]
In this study, we first show that the expression of cardiac miR-128 is lower in neonates than in adults, and is reduced during neonatal heart regeneration. [score:3]
Also at day 7 post AR, genes associated with cell proliferation were significantly activated, whereas miR-128 expression was significantly diminished (Supplementary Fig.   8C, D). [score:3]
Transgenic mice overexpressing miR-128 displayed premature cell cycle exit, cardiac hypertrophy, and cardiac dysfunction. [score:3]
Concomitantly, cell cycle and DNA replication pathways were suppressed in miR-128 [OE] hearts (Supplementary Fig.   3). [score:3]
These data imply that expression level of miR-128 is associated with neonatal heart regeneration. [score:3]
b Schematic of experimental design for CM-specific overexpression of miR-128 at P1 (left panel). [score:3]
Collectively, these data indicate that inhibition of miR-128 promotes CM proliferation and improves endogenous cardiac regeneration after MI (Fig.   10). [score:3]
Fig. 2Overexpression of miR-128 in cardiomyocytes impairs cardiac homeostasis. [score:3]
i Proposed mo del by which miR-128 deletion promotes CM proliferation through coordinating the expression of cell cycle-related genes. [score:3]
Overexpression of miR-128 impairs cardiac homeostasis. [score:3]
The differential expression analysis between miR-128 [OE] hearts and control samples was performed using the negative binomial statistical mo del of read counts as implemented in the edgeR Bioconductor package [53]. [score:3]
Using genetic lineage tracing, our results provide proof-of-concept that pre-existing CMs rather than progenitor cells are, in fact, the target cells that respond to miR-128 deletion during regeneration after cardiac damage. [score:3]
Computational analysis showed that Suz12 was a predicted target gene of miR-128 (Fig.   4a). [score:3]
These data indicate that miR-128 deletion stimulates proliferation of CMs, in part through epigenetic modulation of cell cycle-related genes via targeting of Suz12 (Fig.   5i). [score:3]
In this report, we propose a mo del in which inhibition of miR-128 in vivo promotes cardiac regeneration by activating CM proliferation. [score:3]
Fig. 5 MiR-128 regulates CM proliferation through targeting Suz12. [score:3]
In α-MHC-tTA; miR-128 [TetRE] mice, the TetRE portion of tTA can bind to the TetO sequences after Dox withdrawal, and subsequently induce the CM-specific overexpression of miR-128 (designated as miR-128 [OE] mice) in defined temporal windows (Fig.   2a and Supplementary Fig.   2B). [score:3]
Assessment of miR-128 level by qPCR confirmed its marked overexpression by E10.5 in the hearts of miR-128 [OE] mice (Supplementary Fig.   2F). [score:3]
a The predicted conserved target site of miR-128 in the 3′UTR of Suz12 from different species. [score:3]
f qPCR analysis of miR-128 expression in neonatal (P1) and adult (P28) CMs (n = 5). [score:3]
Expression of Aurora B kinase was markedly elevated in Anti- miR-128 CMs (Supplementary Fig.   4G). [score:3]
Recent research has demonstrated the involvement of miR-128 in cardiac repair of lower vertebrates such as the newt [32] and showed that miR-128 inhibitors enhanced the proliferation (hyperplasia) of non-CMs and extracellular matrix deposition but had no effect on CMs, which was contrary to our current finding in mice. [score:3]
b Expression of Suz12 in miR-128 [−/−] neonatal CMs transfected with either a scrambled control siRNA (si-Ctrl) or Suz12 siRNA (si- Suz12) (n = 5). [score:3]
Peruzzi P MicroRNA-128 coordinately targets polycomb repressor complexes in glioma stem cellsNeuro. [score:2]
A schematic diagram proposing that loss of miR-128 activates cardiac regeneration by promoting cardiomyocyte proliferation, while the necrotic tissue of wild-type heart is replaced by myofibroblasts with fibrous scars in response to MI RNA sequencing (RNA-seq) in mouse cardiac ventricles was performed on postnatal days 1, 7, and 28 (P1, P7, and P28) to identify potential miRNAs involved in the regulation of postnatal heart growth. [score:2]
Tamoxifen (TAM) inducible CM-specific miR-128 knockout mice (i KO) were generated by crossing α-MHC [MerCreMer] mice (Tg(α-MHC-cre/Esr*)1Jmk/J, The Jackson Laboratory) with miR-128 [fl/fl] mice. [score:2]
a Schematic of the experimental design for assessing adult (12-weeks-old) cardiac regeneration following MI in TAM-inducible miR-128 knockout (i KO) mice. [score:2]
The effect of miR-128 knockdown on CM proliferation was then examined using phosphorylated histone 3 (pH3, a marker of mitosis) and Aurora B kinase (a marker of cytokinesis). [score:2]
MiR-128 was robustly upregulated in P7 hearts as compared to P1, which was further confirmed by quantitative PCR (qPCR) array (Supplementary Fig.   1A). [score:2]
Our data suggest that elimination of miR-128 might activate cell cycle-related genes, in part through SUZ12-regulated histone modification, thereby promoting CM proliferation. [score:2]
A construct was engineered for knockin of the miR-128 (miR-128-3p) gene into the Rosa26 locus. [score:2]
To study the role of miR-128 in heart development, miR-128 [OE] mice were mated in the absence of Dox (Supplementary Fig.   2E). [score:2]
After TAM -induced miR-128 deletion (Fig.   7i), the α-MHC myocardial lineage -positive CMs in i KO-tdTomato mouse displayed a disorganized sarcomere structure and reduced sarcomere-related gene expression compared with control mice (α-MHC [MerCreMer]; R26R-tdTomato, designated as Ctrl-tdTomato) (Fig.   7j, k). [score:2]
A further subgroup analysis of the ‘‘cellular process’’ indicated the potential for miR-128 to affect multiple pathways that are related to regulation of the cell cycle, cell communication, and cellular component movement (Supplementary Fig.   7B). [score:2]
The adult miR-128 deleted mice were designated i KO, and the knockout was validated by qPCR. [score:2]
MiR-128 deletion reconfigures cell cycle gene expression. [score:2]
Cardiac-specific conditional miR-128 knockout mice were generated by crossing miR-128 [flox/ flox] (miR-128 [fl/fl]) mice (Supplementary Fig.   5A) with Nkx2.5 [Cre] mice, resulting in cardiac-specific deletion of miR-128 during cardiogenesis (Nkx2.5 [Cre]; miR-128 [fl/fl] mice, designated as miR-128 [−/−]) (Supplementary Fig.   5B). [score:2]
A schematic diagram proposing that loss of miR-128 activates cardiac regeneration by promoting cardiomyocyte proliferation, while the necrotic tissue of wild-type heart is replaced by myofibroblasts with fibrous scars in response to MI The application of direct activation of pre-existing CM proliferation is emerging as one of the most promising strategies in cardiac regenerative medicine 5, 25, 26. [score:2]
a Schematic diagram depicting the generation of cardiac-specific miR-128 knockout (miR-128 [−/−]) mice. [score:2]
In these transgenic mice, the pre-existing CMs with miR-128 knockout were labeled red (tdTomato, red fluorescence) following TAM administration. [score:2]
These data suggest that miR-128 may regulate CM proliferation via its intercation with  Suz12. [score:2]
g Western blot assay for cell cycle-related protein expression in control (miR-128 [fl/fl]), and miR-128 [−/−] (Nkx2.5 [Cre]; miR-128 [fl/fl]) hearts at P7 (n = 5). [score:2]
In our study, miR-128 was revealed for the first time to be a negative regulator of the CM cell cycle when using a cardiac lineage-restricted transgenic mouse mo del. [score:2]
MiR-128 increases during postnatal heart growthRNA sequencing (RNA-seq) in mouse cardiac ventricles was performed on postnatal days 1, 7, and 28 (P1, P7, and P28) to identify potential miRNAs involved in the regulation of postnatal heart growth. [score:2]
TAM was administered at P21 to induce the miR-128 knockout at the adult stage. [score:2]
These data indicate a potential role for miR-128 in regulating CM proliferation. [score:2]
Collectively, our results suggest that miR-128 functions as a critical regulator of endogenous cardiac proliferation and regeneration. [score:2]
e Evaluation of miR-128 expression level during heart development using qPCR analysis, including embryonic day 14.5 (E14.5), E19.5, P1, P3, P7, P14, and P28 hearts (n = 5). [score:2]
i Quantification data of CM proliferative activity by Ki67 staining in Ctrl and miR-128 [OE] hearts (n = 6 mice, ~800 CMs/heart). [score:1]
Control (Ctrl) mice were miR-128 [fl/fl] mice, i KO mice were α-MHC [MerCreMer]; miR-128 [fl/fl] mice. [score:1]
We also found a significant increase in the number of 5-ethynyl-2´-deoxyuridine (EdU) positive CMs in the Anti- miR-128 group indicative of elevated DNA replication (Supplementary Fig.   4H). [score:1]
Control (Ctrl) mice were miR-128 [fl/fl] mice, and i KO mice were α-MHC [MerCreMer]; miR-128 [fl/fl] mice. [score:1]
These results indicate that deletion of miR-128 in the adult heart results in dedifferentiation and cell cycle re-entry of CMs, but has no impact on heart function. [score:1]
Generation of mice with a conditional deletion of miR-128A construct was engineered for conditional disruption of the miR-128 (miR-128-3p) gene in which a 1.7 kb fragment spanning the miR-128 gene was flanked by two loxP sites. [score:1]
α-MHC [MerCreMer] mice were crossed with Rosa26-tdTomato (R26R-mTmG, The Jackson Laboratory) reporter mice and miR-128 [fl/fl] mice to generate i KO-mTmG mice (α-MHC [MerCreMer]; miR-128 [fl/+];R26R-mTmG) to label miR-128 null CM with red color following tamoxifen administration. [score:1]
h Quantification data of p27 mRNA levels in Ctrl and miR-128 [−/−] hearts by qPCR (n = 5). [score:1]
e CM size analysis by WGA and cTnT staining in si-Ctrl and si- Suz12 treated miR-128 [−/−] hearts at P7 (n = 5 mice, ~300 CMs/heart). [score:1]
These miR-128 [OE] mutant mice displayed enlarged heart chambers, myocardial fibrosis, CM hypertrophy, and impaired LV systolic heart function at P28 (Supplementary Fig.   2G–I). [score:1]
f Comparison of EdU [+] CMs in si-Ctrl and si- Suz12 -treated miR-128 [−/−] hearts at P7 (n = 5 mice, ~400 CMs/heart). [score:1]
Fig. 3Cardiac miR-128 deletion promotes postnatal CM proliferation in vivo. [score:1]
This increase in CM number following miR-128 deletion was further confirmed by analysis of EdU incorporation into CMs (Fig.   7e). [score:1]
One day after MI, we administered TAM to delete miR-128 in CMs (Fig.   8a). [score:1]
The i KO-tdTomato mice were αMHC [MerCreMer]; miR-128 [fl/fl]; Rosa [tdTomato]. [score:1]
g, h Western blot analysis of cell cycle-related genes in si-Ctrl and si- Suz12 treated miR-128 [−/−] hearts at P7 (n = 3). [score:1]
This could indicate an increased number of CMs in these hearts due to persistent proliferation resulting from miR-128 deletion. [score:1]
However, there was no significant increase in apoptotic CMs in miR-128 [OE] hearts when assessed by TUNEL staining (Supplementary Fig.   2D). [score:1]
The higher heart-to-body weight ratios (HW/BW) of miR-128 [OE] mice relative to Ctrl showed a progressive increase in heart mass (Fig.   2d). [score:1]
The effect of miR-128 deletion on the cell cycle was evident in adult stages, when adult CMs are fully differentiated and quiescent and their ability to divide is quite limited. [score:1]
A construct was engineered for conditional disruption of the miR-128 (miR-128-3p) gene in which a 1.7 kb fragment spanning the miR-128 gene was flanked by two loxP sites. [score:1]
HEK-293 cells (ATCC, CRL-1573) were transfected using DharmaFECT Duo reagent (Dharmacon, T-2020-01) according to the manufacturer’s instructions with luciferase reporter vector and miR-128 mimic (Dharmacon, C-310957-01-0005). [score:1]
Importantly, an increased level of GATA4 (a marker for dedifferentiated CMs [8]), was observed in Anti- miR-128 CMs (Supplementary Fig.   4I). [score:1]
NS, not significant To determine whether cells in the myocardial lineage dedifferentiate following deletion of miR-128, a TAM inducible dual-lineage tracing system was generated by crossing α-MHC [MerCreMer] mice with miR-128 [fl/fl] mice followed by crossing with Rosa26-tdTomato reporter mice to produce α-MHC [MerCreMer]; miR-128 [fl/+]; R26R-tdTomato mice (designated as i KO-tdTomato) (Fig.   7h). [score:1]
RNA-seq revealed that the downstream genes of miR-128 are involved in pathways of DNA replication, cell cycle, hypertrophic cardiomyopathy, or dilated cardiomyopathy. [score:1]
Staining with WAG, however, showed that the size of the i KO CMs was smaller than the control CMs (Fig.   7b–d), suggesting that loss of miR-128 in the adult heart increases the number of CMs. [score:1]
Although the heart weight-to-body weight ratio (HB/WB) of miR-128 [−/−] and Ctrl mice at P7 was similar (Fig.   3e), the CMs in miR-128 [−/−] hearts were smaller (Fig.   3f). [score:1]
These findings highlight the involvement of miR-128 in the pathway that arrests CM proliferation and cardiac regeneration after birth. [score:1]
The miR-128 [OE] hearts showed fewer proliferating CMs, as quantified by the decreased number of EdU [+] CMs in the injured apex and border area (Fig.   6c, d), and a greater extent of CM hypertrophy (Fig.   6e). [score:1]
While promoting loss of differentiation, silencing of miR-128, did not induce apoptosis in these cells (Supplementary Fig.   4E). [score:1]
We thank Anne Schaefer (Icahn School of Medicine at Mount Sinai, USA) for providing the miR-128 [flox/ flox] mice and Gary E. Shull for manuscript editing. [score:1]
Generation of mice with a conditional deletion of miR-128. [score:1]
These data suggest that tissue-specific deletion of miR-128 deletion is sufficient to extend the postnatal CM proliferation window. [score:1]
This “Tet-off” transgenic mouse (α-MHC-tTA; miR-128 [TetRE]) was produced by crossing α-MHC-tTA mice with miR-128 [TetRE] mice (Supplementary Fig.   2A). [score:1]
The results showed that loss of miR-128 resulted in a striking increase in CM proliferation (Fig.   3g, h). [score:1]
The miR-128 [OE] mice and control miR-128 [TetRE] mice (Ctrl) were subjected to AR at P1, and hearts from both groups were examined histologically. [score:1]
In addition, systolic function was significantly impaired in the miR-128 [OE] group relative to Ctrl group (Fig.   6f, g). [score:1]
Control mice were miR-128 [fl/fl] mice, and miR-128 [−/−] mice were Nkx2.5 [Cre]; miR-128 [fl/fl] mice. [score:1]
To further validate that the Suz12-pathway is a major functional mediator of miR-128 effects, we injected miR-128 [−/−] mice (intraperitoneal (i. p. ) injection) with si- Suz12 or si-Ctrl at P1, P3, P5, and harvested the hearts at P7 (Fig.   5d). [score:1]
In addition to the CMs with disassembled sarcomeres, there was a significantly higher number of Ki67 -positive cells in the miR-128 [−/−] hearts, and with no obvious CM apoptosis in the miR-128 [−/−] hearts (Fig.   3k). [score:1]
The correct integration of loxP sites and the successful removal of the neomycin cassette were confirmed by PCR analysis with the primer listed in Supplementary Table  1. Cardiac-specific miR-128 knockout mice (miR-128 [−/−]) were generated by crossing Nkx2.5 [Cre] (The Jackson Laboratory) mice with miR-128 [fl/fl] mice. [score:1]
The miR-128 gene, under the control of tetO-minimum promoter, was also cloned into the vector between the two homology arms. [score:1]
To determine whether induction of cardiac proliferation following miR-128 deletion in adult mice is sufficient to allow adult heart repair following MI, adult i KO mice were subjected to permanent ligation of the left anterior descending (LAD) coronary artery. [score:1]
However, it remains to be determined whether the effects of miR-128 on cardiac regeneration following injury are mediated in part by its activity in the nervous system. [score:1]
Deletion of miR-128 promotes adult cardiac regeneration. [score:1]
a Schematic diagram depicting the protocol of tamoxifen (TAM)-inducible miR-128 deletion (i KO) in adult hearts (P28). [score:1]
Of particular interest, the changes in cellular capabilities induced by loss of miR-128 result in increased cellular plasticity that allows significant anatomical and functional capacity upon injury, but does not impair heart function under normal conditions. [score:1]
f for wild-type (WT) and mutant Suz12 3′UTR (Mut) in cells treated with either vehicle (Ctrl) or miR-128 mimic (miR-128) (n = 3). [score:1]
Furthermore, the total number of adult CMs and percentage of mono-nucleated CMs was significantly increased in i KO hearts 2 weeks after TAM -induced miR-128 deletion (Fig.   7f, g). [score:1]
Moreover, KEGG pathway analysis showed that oxidative phosphorylation, metabolism, hypertrophic cardiomyopathy, and dilated cardiomyopathy pathways were enriched in miR-128 [OE] hearts. [score:1]
Given the evidence that silencing of miR-128 induces CM proliferation in vitro, we next preceded to determine the effects that deletion of miR-128 would have on CM proliferation in vivo. [score:1]
b Masson trichrome staining of Ctrl and miR-128 [OE] hearts at day 21 after AR. [score:1]
NS, not significant Fig. 10Loss of miR-128 activates endogenous cardiac regeneration. [score:1]
These adult CMs lacking miR-128 can be ‘‘rejuvenated’’ to an immature stage that allows them to dedifferentiate and enter a proliferative state, an endogenous program for natural heart regeneration that occurs in the zebrafish and neonatal mice in response to injury [48]. [score:1]
Deletion of miR-128 prolonged the postnatal CM proliferation window, as evidenced by pronounced sarcomere disassembly and proliferative markers including pH3, Ki67, Aurora B, and EdU. [score:1]
Control mice were miR-128 [TetRE] mice, and miR-128 [OE] mice were α-MHC-tTA; miR-128 [TetRE] mice. [score:1]
NS, not significantTo determine whether cells in the myocardial lineage dedifferentiate following deletion of miR-128, a TAM inducible dual-lineage tracing system was generated by crossing α-MHC [MerCreMer] mice with miR-128 [fl/fl] mice followed by crossing with Rosa26-tdTomato reporter mice to produce α-MHC [MerCreMer]; miR-128 [fl/+]; R26R-tdTomato mice (designated as i KO-tdTomato) (Fig.   7h). [score:1]
Deletion of miR-128 stimulates postnatal CM proliferation. [score:1]
Withdrawal of Dox from miR-128 [OE] fetuses starting at embryonic day 6 (E6) resulted in significant induction of miR-128 in miR-128 [OE] hearts at the P1 neonatal stage as determined by qPCR (Fig.   2b). [score:1]
o Comparison of EdU [+] CMs in Ctrl and miR-128 [−/−] hearts at P21 (n = 6 mice, ~200 CMs/heart). [score:1]
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[+] score: 267
The Msk2 3′UTR reporter was significantly downregulated upon miR-128 overexpression, but was not affected by ARPP21 expression (Supplementary Fig.   8c). [score:8]
The effects of miR-128 overexpression on migration and dendritic complexity could be rescued by co -expression of one of its regulatory targets, the intellectual disability syndrome gene Phf6 6, 14. [score:8]
g, h Quantification of PHF6 and MSK1 protein expression from five independent experiments as in f. * p < 0.05, *** p < 0.001, one-sample t-test against 100%, data represents mean ± s. d. i miR-128 overexpression by lentivirus in primary cortical neurons at DIV7 reduces MSK1 and PHF6 protein expression. [score:7]
We previously showed that Phf6 expression is inhibited by miR-128 during corticogenesis and that PHF6 can rescue the miR-128 overexpression phenotype of reduced dendritic complexity in upper-layer neurons [6]. [score:7]
miR-128 -loaded miRISC binds and downregulates target mRNAs that possess the miR-128 seed match sequence. [score:6]
ARPP21 is upregulated in mouse miR-128 loss-of-function mutants [13], most likely through a conserved binding site for miR-128 in the Arpp21 3′ untranslated region (UTR; Supplementary Table  1b; Supplementary Fig.   1a). [score:6]
These results prompted us to compare the KEGG pathways for ARPP21 targets with that of 1132 mRNAs predicted to harbor conserved miR-128 binding sites as determined by the TargetScan 7.1 database [32]. [score:5]
a, b Conserved TargetScan predictions for miR-128 -binding sites (orange bars) and ARPP21 iCLIP CL signals (turquoise) at the 3′UTRs of the miR-128 target mRNAs Phf6 and Msk1. [score:5]
a Venn diagram of conserved TargetScan 7.1 miR-128 target mRNAs, and ARPP21 iCLIP substrate mRNAs. [score:5]
It was therefore surprising that ARPP21 does the opposite and antagonizes the inhibitory effect of miR-128 on several functionally important targets of miR-128, such as Phf6 and Upf1. [score:5]
Fig. 8Schematic depiction of our mo del for the miR-128-ARPP21 regulatory circuit and its impact on the post-transcriptional regulation of common mRNA targets. [score:5]
Further, miR-128 can inhibit Arpp21 expression through a conserved seed match in the Arpp21 3′UTR. [score:5]
d miR-128 and poly-U 7mer occurrence normalized per kilobase of 3′UTR comparing ARPP21 target and non-target transcripts. [score:5]
ARPP21 binds and stimulates the expression of a subset of miR-128 target mRNAs (Fig.   8a). [score:5]
ARPP21 binds a subset of miR-128 target mRNAs via a uridine-rich sequence motif leading to increased protein expression. [score:5]
miR-128 represses and ARPP21 increases GFP reporter expression; co-transfection leads to intermediate expression. [score:5]
As a negative control we chose Msk2, a predicted target of miR-128 that is expressed at comparable levels to its paralog Msk1 in iARPP21 cells but without detectable binding in the iCLIP experiment (Supplementary Data  4). [score:5]
These results suggest that at least some of the regulatory activities of ARPP21 and miR-128 may converge on a shared set of target genes. [score:4]
This significantly impaired transactivation of the deletion mutant compared to the wild-type construct by ARPP21 but did not affect either basal expression or suppression by miR-128 (Supplementary Fig.   9b, c). [score:4]
However, it likely represents a functionally important target within a network of co-regulated mRNAs that are sensitive to the balance between miR-128 and ARPP21 activity. [score:4]
During cortex development miR-128 inhibits migration and limits dendritic growth and complexity of upper-layer neurons [6]. [score:4]
Since ARPP21 and miR-128 are derived from a single transcriptional unit, this raises the question of how the balance between the inhibitory functions of miR-128 and the activating functions of ARPP21 is regulated. [score:4]
Co -expression of ARPP21 and miR-128 in this assay led to intermediate protein expression (Fig.   6f–h). [score:4]
To analyze Arpp21 function in neurons we used lentiviral -mediated knockdown of Arpp21 and overexpression of miR-128 and ARPP21 in primary cortical neuron cell cultures. [score:4]
The abundance of the Phf6 and the Msk1 transcripts declines between E16 and P1, consistent with developmental targeting of the miR-128 binding sites present in their 3′UTRs. [score:4]
To test our mo del of functional antagonism between miR-128 and ARPP21 in development we chose the intellectual disability gene Phf6 as a highly ranked ARPP21 target in the iCLIP experiment. [score:4]
Overexpression of miR-128 in upper-layer cortical neurons during embryonic development leads to a significant reduction in the dendritic arborization of the affected neurons, an effect that is largely mediated by PHF6 [6]. [score:4]
The 3′UTRs of ARPP21 target mRNAs harbor a significantly higher number of miR-128 7mer seed sequences compared to non-target mRNAs (Fig.   5c, left panel). [score:4]
Fig. 6ARPP21 and miR-128 have antagonistic functions on an overlapping set of target mRNAs. [score:3]
To validate the iCLIP results, we therefore focused on predicted ARPP21 targets with known functions downstream of miR-128 in the nervous system. [score:3]
Quantification of miR-128 expression by quantitative reverse transcription-PCR (qRT-PCR) revealed an ≈200-fold increase from embryonic day 12 (E12) to postnatal stages (Supplementary Fig.   1c), confirming an earlier northern blot analysis [22]. [score:3]
b Co-regulated transcripts have a greater dynamic range of gene expression compared to transcripts under control of either miR-128 or ARPP21 acting on their own. [score:3]
On the other hand, miR-128 processing is regulated during development. [score:3]
Common targets but opposing functions of ARPP21 and miR-128. [score:3]
Possibilities include the suppression of miR-128-2 precursor processing in neurogenic progenitors, which might represent a timing mechanism to delay miR-128 accumulation relative to the ARPP21 protein [6]. [score:3]
j Quantification of miR-128 overexpression effect on MSK1 and PHF6 protein levels. [score:3]
Fig. 5ARPP21 and miR-128 bind an overlapping set of target mRNAs with related functions. [score:3]
Importantly, co -expression of miR-128 reversed the effects of ARPP21 (Supplementary Fig.   18a-c, complete set of neurons in Supplementary Fig.   19 and 20), indicating that the two exert their effects on dendrite morphogenesis via common pathways. [score:3]
The extensive degree of co-regulation we report between miR-128 and ARPP21 is likely to be important for the physiological roles of miR-128 in cortical development and neuronal excitability. [score:3]
This suggests that the motif is a valid proxy for ARPP21 -binding, but the association with miR-128 sites may be subject to more complex co-dependency between 3′UTR length and miRNA targeting (reviewed in ref. [score:3]
3′UTRs of ARPP21 and miR-128 target genes were cloned into a modified peGFP-C1 backbone, carrying an in-frame stop codon before the multiple cloning site [44]. [score:3]
The substantial overlap between transcripts with binding sites for miR-128 and ARPP21 was surprising, given their opposite activities in post-transcriptional gene expression. [score:3]
Although increased miR-128 expression could block the effect of ectopic ARPP21 on dendrites, it seems unlikely that Phf6 is solely responsible for these in vivo effects. [score:3]
miR-128 -mediated silencing was observed for all the 3′UTR constructs, confirming previously published results 6, 11, 34 or TargetScan predictions [32]. [score:3]
A negative feedback loop caused by the ability of miR-128 to suppress the ARPP21 mRNA might subsequently promote a rapid switch between the two activities. [score:3]
CASC3, MSI2, and UPF1 are components of the NMD pathway subject to inhibition by miR-128 during neuronal differentiation [11]. [score:3]
For example, the NMD and MAP-kinase signaling pathways are known to be inhibited by miR-128 11, 13 and are also enriched for ARPP21-bound mRNAs. [score:3]
The binding repertoire of ARPP21 we observed, however, is by no means restricted to downstream targets of miR-128. [score:3]
for Phf6 and Msk1, the strongest miR-128 targets, are in Fig.   6d, e, all others in Supplementary Fig.   8b. [score:3]
PHF6 was previously shown to be targeted by miR-128 during cortical neuron migration and dendritogenesis [6]. [score:3]
A better understanding of how miR-128 activity is regulated would provide insight into how miR-128 can perform its multiple developmental functions. [score:3]
a ARPP21 and miR-128 are co-expressed from the same genetic locus. [score:3]
Dendritic complexity of cortical neurons is highly sensitive to the relative levels of miR-128 and ARPP21 Our finding that ARPP21 preferentially binds 3′UTRs suggests that it antagonizes miRNA function in general and miR-128 targeting in particular. [score:3]
d, e Phf6 and Msk1 3′UTR reporter fluorescence upon miR-128 and/or ARPP21 expression normalized to control transfection. [score:3]
Developmental regulation of the miR-128 host genes. [score:3]
miR-128 mimic transfection results in reduced expression of MSK1 and PHF6 protein. [score:3]
Full-length ARPP21 protein levels steadily increased during mouse brain development (Fig.   1e), comparable to miR-128 (Supplementary Fig.   1c). [score:2]
Exogenous ARPP21 had the opposite effect as miR-128 and significantly increased GFP expression, consistent with the results obtained with the tethering assay. [score:2]
However, this does not necessarily imply direct interference with miRNA binding, as we did not observe a statistically significant bias for ARPP21 -binding in the vicinity of miR-128 seed sequences (Supplementary Fig.   7d). [score:2]
Significantly enriched KEGG pathways included mRNA surveillance, a pathway involving nonsense -mediated decay (NMD) that was previously shown to be regulated by miR-128 [11] (Supplementary Fig.   6b, c; Supplementary Data  1). [score:2]
Our results reveal that miR-128 is not only physically but also functionally embedded in a previously unrecognized post-transcriptional regulatory circuit involving its host genes. [score:2]
Mechanisms that could potentially regulate the relative activities of ARPP21 and miR-128 are marked in red. [score:2]
MSK1 and CREB1 are part of the activity -dependent signaling cascade that is perturbed in miR-128 -knockout animals 13, 34. [score:2]
Together, the results of these experiments suggest that cortical dendritic arbors are highly sensitive to ARPP21 dosage during the late embryonic and postnatal stages of growth, and suggest that miR-128 is a negative and ARPP21 a positive regulator of this process. [score:2]
The functional overlap of miR-128 and ARPP21 might not be restricted to dendritic morphogenesis. [score:1]
Loss of miR-128 function in mice causes neuronal hyperexcitability accompanied by severe and lethal seizures [13]. [score:1]
The overlap between transcripts harboring miR-128 and ARPP21 -binding sites (256) was significantly higher than predicted by chance (Fig.   5a) and enrichment analysis performed on this set of transcripts recovered similar pathways, including mRNA surveillance, neurotrophin, TGF-β, and MAP-kinase signaling (Table  1; Supplementary Fig.   6e; Supplementary Data  3). [score:1]
Next, we wanted to test if the molecular antagonism between ARPP21 and miR-128 might be relevant to known functions of miR-128 in vivo. [score:1]
We selected Phf6, Msk1, Creb1, Upf1, and Casc3 for further analysis; their iCLIP signals and conserved miR-128 -binding sites are described in Fig.   6a, b and Supplementary Fig.   8a. [score:1]
miR-128 is one of the most abundant miRNAs in cortical neurons [41], and is one of the few mammalian miRNAs with a lethal phenotype upon deletion [13]. [score:1]
This closely corresponds to the pattern seen for miR-128 at this stage [6]. [score:1]
Mammals have two genes for miR-128 that are located in introns of two conserved, orthologous protein-coding host genes, R3hdm1 and Arpp21, that harbor miR-128-1 and miR-128-2, respectively. [score:1]
Other enriched KEGG terms with known links to miR-128 function were transforming growth factor-β (TGF-β) [31] and neurotrophin signaling pathways that may be related to the dendritogenesis and hyperexcitability phenotypes of miR-128 6, 13. [score:1]
As expected, miR-128 significantly reduced both the protein and mRNA levels of neuronal Phf6 and Msk1 mRNAs (Fig.   6i, j and Supplementary Fig.   14a-c). [score:1]
Full western blot images are presented in Supplementary Fig.   21 To begin the characterization of ARPP21, we compared its expression pattern in mouse brain development to miR-128. [score:1]
Transfection of a synthetic miR-128 mimic led to reduced protein levels of PHF6 and MSK1, ectopic ARPP21 had the opposite effect. [score:1]
ARPP21 opposes miR-128 functions in dendritic growth in vivo. [score:1]
The miRNAs chosen include highly conserved and ubiquitous miRNAs (let-7, miR-125) as well as representative tissue-specific miRNAs from stem cells (miR-302), muscle (miR-1), blood (miR-150), and nervous system (miR-9, miR-124, miR-128, miR-132, and miR-138). [score:1]
Full western blot images are presented in Supplementary Fig.   21To begin the characterization of ARPP21, we compared its expression pattern in mouse brain development to miR-128. [score:1]
a Genomic localization of murine miR-128 within the host genes Arpp21 and R3hdm1. [score:1]
After normalizing for UTR length, enrichment for the poly-U motif but not miR-128 sites retains statistical significance (Fig.   5d). [score:1]
pri-miR-128-2 is generated upon Arpp21 transcription and subsequently processed by Drosha and Dicer into mature miR-128. [score:1]
ARPP21 binds and transactivates the mRNAs for a number of well-characterized targets for miR-128 -mediated silencing, including Phf6. [score:1]
The two miR-128 isoforms differ in respect to their stem-loop precursor sequences but yield identical mature 22-nt RNAs [15]. [score:1]
c Number of occurrences of miR-128 seed matches and poly-uridine (poly-U) 7mers per 3′UTR among ARPP21-bound and ARPP21-unbound transcripts. [score:1]
293T cells were reverse transfected with empty intron-RED vectors with or without intron-RED-miR-128-2 [6] and p3xFLAG-CMV-7.1 vectors with or without murine ARPP21. [score:1]
c Schematic of 3′UTR GFP-reporter assay to assess direct effects of miR-128 and ARPP21 on individual transcripts. [score:1]
The gene structure of the two mouse miR-128 host genes is shown in Fig.   1a. [score:1]
P. K. performed miR-128 gain-of-function experiments in neurons, in utero electroporations for the Supplementary Information, and prepared the primary neuronal cultures. [score:1]
Of these, the miR-128 seed match was the most abundant, followed by the other brain-enriched miRNAs (Fig.   5b). [score:1]
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Figure 7A-7E illustrates that the mRNAs expression levels of Bmi-1, Szrd1, and Aff4 between WT and miR-128-2 -overexpressed CLP did not differ, although the mRNA expression levels of A2B and MALT1 were obviously downregulated in miR-128-2 -overexpressed CLP compared with those in WT CLP. [score:11]
To further explain the molecular mechanism by which miR-128-2 affects the apoptosis of CLP, we attempted to seek for relevant targets of miR-128-2. Although some key TFs play pivotal roles in B cell development, such as RAG, AFF4, Bmi-1, IKZF3, RBPJ, BCL2L11, Dclrec, and PTEN, no difference was observed in their expression levels between WT and miR-128-2 -overexpressed B cells or CLPs (Figure 7 and data not shown). [score:8]
MiR-128-2 overexpression could inhibit the apoptosis of CLP by regulating the ERK and P38MAPK pathways via targeting the A2B and MALT1 genes. [score:7]
To investigate whether upregulated expression of miR-128-2 can alter the development of lymphocytes, we adopted the miR-128-2 -overexpressed chimera and TG mice mo dels. [score:7]
Further studies suggested that miR-128-2 overexpression did not alter the proliferation or apoptosis of preproB, proB, and preB, but inhibited CLP to develop into preproB cells, partially caused by blocking the apoptosis of CLP. [score:5]
MiR-128-2 overexpression leads to inhibition of B cell development. [score:5]
Our study also found that miR-128-2 may also target MALT1 in CLPs in combination with A2B to regulate CLP development through the ERK and p38 MAPK pathways. [score:5]
Our further studies will focus on whether abnormal expression of miR-128-2 is associated with certain lymphoid diseases in clinical settings. [score:5]
By establishing the miR-128-2 -overexpressed chimera and TG mice mo dels, we found that miR-128-2 -overexpressed mice showed a reduction in preproB, proB, preB, and immature B cells in the BM. [score:5]
Although miR-128-2 was significantly differentially expressed in different subsets of T cells (Figure 1B), these subsets were not affected in miR-128-2 -overexpressed chimera mice or in miR-128-2 sponge chimera mice (Supplementary Figure 3 and data not shown). [score:5]
Our study found that miR-128-2 could inhibit the apoptosis of CLP by targeting A2B. [score:5]
To determine whether miR-128-2 directly targets A2B and MALT1 for repressing gene expression, we first conducted the luciferase report assay to verify whether miR-128-2 can bind to the 3′-UTR of A2B and MALT1. [score:5]
Luciferase assays showed that miR-128-2 could bind to the 3′-UTR of A2B and MALT1 and downregulate the expression of luciferase (Figure 7F-7H). [score:5]
In this study, we first found that miR-128-2 was differentially expressed in B cells at different stages of development from CLP to mature B cells. [score:4]
The heat map in Supplementary Figure 1 shows that miR-128 was highly expressed in DP thymocytes relative to other detected cells, which aroused our curiosity in the function of miR-128-2 in the development of immunocytes. [score:4]
In summary, our study suggested that mir-128-2, which is highly expressed in progenitor and immature lymphocytes, regulated CLP to develop into preproB cells. [score:4]
These data strongly suggested that overexpressed miR-128-2 directly blocked CLP from developing into preproB cells. [score:4]
Annexin V staining and BrdU incorporation assay revealed that overexpressing miR-128-2 inhibited the apoptosis of CLP, but did not affect the proliferation of CLP. [score:4]
These results strongly suggested that A2B and MALT1 were the target genes of miR-128-2, which indicated that these two genes might be involved in the decreased apoptosis of CLP and development of CLP to preproB cells. [score:4]
By establishing miR-128-2 chimera and TG mice mo dels, we found that ectopic expression of miR-128-2 could impair B cell development. [score:4]
In the present study, we found that miR-128 was differentially expressed among various immunocytes, which indicated that miR-128 may also be involved in the development of lymphocytes. [score:4]
Given that miR-128-2 was overexpressed in all the body cells of TG mice, the possibility that the effect of miR-128-2 on B cell development might be indirectly through other cells must be considered. [score:4]
By screening the checkpoints of B cell development, we found that overexpression of miR-128-2 blocked CLPs from developing into preproB cells. [score:4]
These results strongly suggested that miR-128-2 inhibited the development of B cells. [score:4]
Total B cells and B cell subsets were reduced in BM of miR-128-2 overexpressed chimera mice. [score:3]
Further experiments demonstrated that miR-128-2 might exert this function by targeting A2B and MALT1, thereby affecting the phosphorylation of ERK and p38 MAPK. [score:3]
To explore the underlying mechanisms of miR-128-2 function in the apoptosis and differentiation of CLP, we used miRWalk software to predict the target genes of miR-128 and select those that can be predicted by more than five programs. [score:3]
However, the frequency of apoptotic cells in miR-128-2 -overexpressed CLP was lower than that in WT CLP (Figure 6C, 6D). [score:3]
Supplementary Figure 2C indicated that miR-128-2 was successfully overexpressed in miR-128-2 TG mice. [score:3]
The phenotypes of miR-128-2 TG mice were not completely consistent with MALT1 -deficient mice, which may be due to miR-128-2 targeting multiple genes in CLP [31, 32]. [score:3]
We found that the percentages of total T cells and all T cell subsets, including DN, DP, CD4, or CD8 SP, were similar between WT and miR-128-2 -overexpressed chimera mice (Supplementary Figure 3). [score:3]
Expression of miR-128-2 in different immune organs. [score:3]
com) to further investigate through which pathways A2B, MALT1, or other potential targets are involved in the apoptosis of miR-128-2 -overexpressed CLP, as well as to analyze the signaling pathways that may be mediated by them. [score:3]
Supplementary Figure 8 and 9 shows that miR-128-2 did not change the proliferation and apoptosis of preproB cells, thereby indicating that decreased apoptosis was responsible for the increase in CLP in miR-128-2 -overexpressed mice. [score:3]
Assessing the target genes of miR-128-2 in apoptosis of CLP. [score:3]
Further analysis showed that both ALP and BLP increased in miR-128-2 -overexpressed TG mice without alteration in their ratio in CLP (Figure 4 and Supplementary Figure 6). [score:3]
Figure 5MiR-128-2 -overexpressed CLP developed less B cells in the in vitro B cell culture systemCLP cells were sorted from WT or miR-128-2 TG mice and cultured as described in M&M. [score:3]
The overexpression of miR-128-2 did not alter the percentages of HSC and MPP, but increased the percentage of CLP and decreased the percentages of preproB, proB, immature B cells, and recirculating B cells. [score:3]
However, apoptosis significantly decreased in miR-128-2 -overexpressed CLP, which may result in the increase in percentage of CLP and block CLPs from further differentiating into preproB cells. [score:3]
Moreover, abnormal expression levels of miR-128 were detected in several cancer patients. [score:3]
Identification of target genes of miR-128-2. MiR-128-2 affects CLP apoptosis through the ERK and p38 MAPK signaling pathways. [score:3]
This result suggested that miR-128-2 overexpression resulted in hyperactive ERK and p38 signaling pathways, which may cause decreased apoptosis of CLPs. [score:3]
To determine which checkpoint miR-128-2 affects during B cell development, we compared HSC, MPP, and CLP levels between WT and miR-128-2 -overexpressed TG mice. [score:3]
To validate miRNA targets, approximately 10 [5] 293T cells per well in a 24-well plate were transiently transfected with 0.3μg of each firefly luciferase reporter construct, 0.1μg of Renilla luciferase TK vector, and 0.6μg of pMSCV-miR-128-2 or control vector of pMSCV-miR-130 or pMSCV-miR-29b2. [score:3]
We observed that the ratio of ALP and BLP did not change between WT and miR-128-2 -overexpressed CLPs. [score:3]
Western blot experiments demonstrated that the protein levels of A2B and MALT1 were both significantly lower in miR-128-2 -overexpressed B220 [+]IgM [−] preproB cells than those in WT cells (Figure 7I). [score:3]
No difference in BrdU incorporation between WT and miR-128-2 -overexpressed CLP (Figure 6A, 6B) was found. [score:3]
MiR-128 is highly expressed in the brain and has been reported to play key roles in the development of the nervous system and maintenance of its normal physical functions [26]. [score:3]
After confirming the successful overexpression of miR-128-2 in 293T cells and chimera mice by real-time PCR or Northern blot (Supplementary Figure 2A, 2B), we prepared single-cell suspensions from BM, spleen, and thymus of two- to three-month-old chimera mice for flow cytometric analysis. [score:3]
MiR-128-2 -overexpressed TG mice have reduced total B cells and B cell subsets, including preproB, proB, preB, immature B, and recirculating B cells. [score:2]
However, the percentages of total B220 [+] cells and B cell subsets, including preproB (B220 [+]IgM [−]), immature B, and recirculating B cells, were significantly reduced in miR-128-2 -overexpressed chimera mice compared with those in WT mice (Figure 2). [score:2]
MiR-128-2 was differentially expressed in various immune organs and immunocytes. [score:2]
To detect miR-128-2 expression, total RNAs were reversed using MMLV reverse transcriptase with miR-128-2 specific RT primer 5′-CTC AAC TGG TGT CGT GGA GTC GGC AAT TCA GTT GAG AAA GAG AC-3′. [score:2]
MiR-128-2 inhibits the apoptosis of CLP. [score:2]
The proliferation of miR-128-2 -overexpressed CLPs also did not change compared with that of WT CLPs. [score:2]
Phosphorylation of ERK and p38 MAPK was enhanced in miR-128-2 -overexpressed CLP compared with those in WT CLP. [score:2]
However, this hypothesis for the miR-128-2 knockout mice mo del requires further confirmation. [score:2]
Nevertheless, luciferase assay and real-time PCR combined with Western blot suggested that MALT1 and A2B were the target genes of miR-128-2 in CLPs. [score:2]
These data suggested that miR-128-2 may be involved in lymphocyte development. [score:2]
MiR-128-2 -overexpressed CLP developed less B cells in the in vitro B cell culture system. [score:2]
Thus, miR-128-2 for T cell development may be redundant. [score:2]
Our in vivo and in vitro experiments showed that miR-128-2 may impair B cell development by blocking CLP to further develop into preproB cells. [score:2]
Intracellular staining revealed that phosphorylation of ERK and p38 MAPK was obviously enhanced in miR-128-2 -overexpressed CLP compared with that in WT CLPs (Figure 8). [score:2]
Total RNAs were extracted from 293T or pMSCV-miR-128-2 -transfected 293T cells for the detection of miR-128-2 expression using a highly sensitive miRNA Northern blot assay kit (Signosis, Inc. [score:2]
Numerous studies have demonstrated that miR-128 can regulate the proliferation, differentiation, and apoptosis of various tumor cells [27]. [score:2]
However, whether miR-128 is also involved in lymphocyte development is largely unknown. [score:2]
As shown in Figure 1, miR-128-2 expression was higher in central immune organs (BM and thymus) compared with that in the spleen (Figure 1A) and then decreased progressively as T or B cells developed (Figure 1B and 1C). [score:2]
B cell development in vitroSingle-cell suspensions from BM of WT or miR-128-2 TG mice were prepared and then stained with anti-IL-7R-PE, anti-ckit-pecy7, anti-Sca1-APC, and lineage antibodies (pacific blue-labeled anti-CD3, CD4, CD8, CD11c, CD11b, B220, NK1.1, Gr1, and Ter-199 antibodies). [score:2]
was adopted to evaluate the expression of Bmi-1, Szrd1, Aff4, A2b, and Malt1 A. - E. ; Luciferase assays were conducted to measure the inhibition of miR-128-2 on the expression of MALT1 F. and A2B G. and H.. [score:2]
Figure 4BM from 6-8 week-old WT or miR-128-2 TG mice were prepared and stained with relative antibodies (as described in M&M) followed by FACS analysis. [score:1]
To explain the increase in CLP in miR-128-2 -overexpressed mice, we measured the proliferation or self-renewal and apoptosis of CLPs by BrdU incorporation and annexin V staining, respectively. [score:1]
To test this hypothesis, we sorted CLPs from BM of miR-128-2 TG mice or WT mice by FACS and observed cell differentiation in an in vitro culture system as described in the literature [24, 25]. [score:1]
Single-cell suspensions from BM of wild-type (WT) and miR-128-2 TG mice were prepared for staining with specific fluorescence-conjugated antibodies. [score:1]
Figure 3BM from 6-8 week-old WT or miR-128-2 TG mice were prepared and stained with relative antibodies followed by FACS analysis. [score:1]
To verify whether the reduction of preproB, proB and preB cells is possible due to miR-128-2 affecting these cells themselves, we further analyzed the ratio of preproB, proB and preB cells in B220 [+]IgM [−] B cells in BM, the results showed that the ratio of preproB, proB and preB cells in B220 [+]IgM [−] B cells between WT and miR-128-2 TG mice was not significantly changed (Supplementary Figure 7). [score:1]
BM from 6-8 week-old WT or miR-128-2 TG mice were prepared and stained with relative antibodies (as described in M&M) followed by FACS analysis. [score:1]
To eliminate the possibility that the decrease in preproB cells was due to miR-128-2 affecting the preproB cells themselves, we detected the proliferation and apoptosis of preproB cells via BrdU and annexin V staining. [score:1]
Preparation of miR-128-2 chimera and TG mice mo dels. [score:1]
BM from 6-8 week-old WT or miR-128-2 TG mice were prepared and stained with relative antibodies followed by FACS analysis. [score:1]
To further confirm the phenotypes in chimera mice, we generated the miR-128-2 TG mice as described in the Materials and Methods. [score:1]
Infected cells were resuspended in PBS and then injected i. v. into lethally irradiated (8.5Gy) recipient mice to establish the miR-128-2 chimera mice mo del. [score:1]
The plasmids pMSCV_GW_RfA_PGK_EGFP-miR-128-2, pMSCV_GW_RfA_PGK_EGFP-miR-130, and pMSCV_GW_RfA_PGK_EGFP-miR-29b2 (hereafter called pMSCV-miR-128-2, pMSCV-miR-130, and pMSCV-miR-29b2, respectively) encoding mature miR-128-2, miR-130, and miR-29b2, respectively, were provided by Dr. [score:1]
CLP cells were sorted from WT or miR-128-2 TG mice and cultured as described in M&M. [score:1]
Single-cell suspensions from BM of WT or miR-128-2 TG mice were prepared and then stained with anti-IL-7R-PE, anti-ckit-pecy7, anti-Sca1-APC, and lineage antibodies (pacific blue-labeled anti-CD3, CD4, CD8, CD11c, CD11b, B220, NK1.1, Gr1, and Ter-199 antibodies). [score:1]
The results showed that the percentage of CLP was higher in miR-128-2 TG mice than that in WT mice without significant changes in earlier cells, such as HSCs and MPPs (Figure 4). [score:1]
FACS analysis revealed that miR-128-2 TG mice displayed similar phenotypes to those in miR-128-2 chimera mice, that is, reduction in B220 [+]IgM [−] B cells (including preproB, preB and proB cells), immature B cells, and recirculating B cells in BM, without changes in T cells, cDCs, and MDSCs (Figure 3 and Supplementary Figure 4). [score:1]
The generation of miR-128-2 TG mice pMSCV-128-2 plasmids was first linearized by HindIII restriction enzyme digestion and then micro -injected into ES cells with C57/BL6 background. [score:1]
Figure 7Real-time PCR assay was adopted to evaluate the expression of Bmi-1, Szrd1, Aff4, A2b, and Malt1 A. - E. ; Luciferase assays were conducted to measure the inhibition of miR-128-2 on the expression of MALT1 F. and A2B G. and H.. [score:1]
To further verify the microarray data, we prepared total RNA from organs (including BM, thymocytes, and spleen) and purified lymphocytes (including DP and DN thymocytes from thymus, CD4 [+] and CD8 [+] single -positive T cells from spleen, CLP, preproB, immature B cell, and recirculating B cells from BM) to measure miR-128-2 expression by real-time PCR. [score:1]
As shown in Supplementary Figure 10, miR-128-2 may be involved in the AKT, p38 MAPK, NF-κb, and Fos pathways. [score:1]
Six- to eight-week-old miR-128-2 TG mice were used for the experiments. [score:1]
The miR-128-2 TG mice used in this study were generated by Cyagen Bioscience, Inc(Guangzhou, China). [score:1]
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4
[+] score: 211
Murine miR-128, miR-134, and miR-330 directly target and inhibit Mmp3, Mmp10, and Mmp13, respectivelyTo predict whether miRNAs target Mmp3, Mmp10, and/or Mmp13 in murine colon cancer cells, we first utilized the bioinformatics algorithms TargetScan, miRWalk, microRNA. [score:10]
We found that knockdown of Dicer1 expression resulted in downregulation of miR-128/miR-134/miRNA-330 and upregulation of Mmp3/Mmp10/Mmp13 (Figure 4C). [score:10]
Then we asked whether down-regulation of Dicer1 led to down-regulation of miR-128, miR-134 and miRNA-330, and consequently up-regulation of Mmp3/Mmp10/Mmp13 particularly? [score:10]
Furthermore, we indicated that knockdown of Dicer1 resulted in downregulation of miR-128/miR-134/miRNA-330 and upregulation of Mmp3/Mmp10/Mmp13 (Figure 4C). [score:8]
MiR-128, miR-134, and miR-330 suppress the tumorigenicity of murine colon cancer cells in vitro and in vivoSince miR-128, miR-134, and miR-330 can target Mmp3, Mmp10, and Mmp13, respectively and are downregulated in the inflammation-cancer link, we next explored the functions of miR-128, miR-134, and miR-330 with respect to their contributions to the tumorigenic potential of the CT26. [score:8]
Gapdh was used as the internal control, and the expression values of “mimics or inhibitor control” were set as 1. (D) Transfection with miR-128, miR-134, or miR-330 mimic decreased Mmp3, Mmp10, and Mmp13 protein levels, respectively, whereas transfection with the miR-128, miR-134, or miR-330 inhibitor increased Mmp3, Mmp10, and Mmp13 levels, respectively, in CT26. [score:7]
Figure 5miR-128, miR-134, and miR-330 suppress the tumorigenicity of murine colon cancer cells and inhibit tube formation of endothelial cells in vitro (A) showing that miR-128, miR-134, and miR-330 suppressed the migration of CT26. [score:7]
Because overexpression of miR-128, miR-134, or miR-330 could inhibit tumorigenesis in vitro, we next asked whether these miRNAs could inhibit the metastatic potential of CT26. [score:7]
Murine miR-128, miR-134, and miR-330 directly target and inhibit Mmp3, Mmp10, and Mmp13, respectively. [score:6]
These results provided evidence that each of miR-128, miR-134, and miR-330 directly recognizes the respective 3′-UTR of the Mmp3, Mmp10, and Mmp13 mRNAs and thereby inhibits their translation. [score:6]
Since miR-128, miR-134, and miR-330 can target Mmp3, Mmp10, and Mmp13, respectively and are downregulated in the inflammation-cancer link, we next explored the functions of miR-128, miR-134, and miR-330 with respect to their contributions to the tumorigenic potential of the CT26. [score:6]
To verify whether Mmp3, Mmp10, and Mmp13 are direct targets of miR-128, miR-134, and miR-330, respectively, we used a luciferase assay to test the binding of each miRNA to the respective gene's 3′ untranslated region (UTR). [score:5]
WT cells overexpressing miR-128, miR-134, or miR-330 inhibited tube formation. [score:5]
Overexpression of the miR-128, miR-134, or miR-330 mimic clearly delayed wound gap closure compared with each mimic control, whereas knockdown of miR-128, miR-134, or miR-330 using the corresponding miRNA inhibitor had the opposite effect (Figure 5A). [score:5]
These observations suggested that miR-128, miR-134, and miR-330 can suppress the migration, invasion, and proliferation of murine colon cancer cells in vitro and that they also can inhibit endothelial cell tube formation to some extent. [score:5]
A total of 3761, 1020, and 1686 possible targets for miR-128, miR-134, and miR-330, respectively, were predicted by TargetScan, miRWalk, and miRanda. [score:5]
We then used DAVID Resources Analysis Tools to classify the function of these target genes, revealing that most target genes of miR-128, miR-134, and miR-330 are involved in signaling pathways such as MAPK, Wnt, TGF-β, and mTOR and in the function of adherens junctions (Figure 3C), all of which are important for tumorigenesis. [score:5]
miR-128, miR-134, and miR-330 suppress the tumorigenicity of murine colon cancer cells and inhibit tube formation of endothelial cells in vitro. [score:5]
The mechanism responsible for the downregulation of miR-128, miR-134, and miR-330 during CAC progression. [score:4]
The matrigel invasion assay showed that overexpression of the miR-128, miR-134, or miR-330 mimic inhibited the in vitro invasive potential of CT26. [score:4]
Figure 3 Mmp3, Mmp10, and Mmp13 are direct targets of murine miR-128, miR-134, and miR-330, respectively (A) Scheme for the potential binding site of miR-128, miR-134, and miR-330 in the 3′-UTR of Mmp3, Mmp10, and Mmp13 and the sequence of each intact miR-128, miR-134, and miR-330 binding site (wild-type, wt) and its mutant (Mut) within the luciferase reporter vector. [score:4]
Inflammation -dependent downregulation of miR-128, miR-134, and miR-330 during murine CAC progression and an inverse correlation with the levels of Mmp3, Mmp10, and Mmp13. [score:4]
Mmp3, Mmp10, and Mmp13 are direct targets of murine miR-128, miR-134, and miR-330, respectively. [score:4]
As shown in Figure 5C, overexpression of the miR-128, miR-134, or miR-330 mimic attenuated CT26. [score:3]
WT cells with miR-128, miR-134, or miR-330 mimics resulted in decreased expression of Mmp3, Mmp10, or Mmp13, respectively, within the resulting tumors. [score:3]
We identified seven murine miRNAs (miR-128, 134, 143, 330, 350, 692, 743a) that were predicted to target Mmp mRNAs by at least two of the four algorithms (Figure 2A). [score:3]
These results indicated that miR-128, miR-134, and miR-330 can suppress the metastasis of murine colon cancer cells to lung. [score:3]
These results suggested that murine miR-128, miR-134, and miR-330 target Mmp3, Mmp10, and Mmp13, respectively. [score:3]
Transfection of cells with Mmp3, Mmp10, or Mmp13 rescued the angiogenic capabilities of cells overexpressing miR-128, miR-134, or miR-330. [score:3]
We next searched for possible target genes of miR-128, miR-134, and miR-330 using web -based bioinformatics algorithms. [score:3]
miR-128, miR-134, and miR-330 suppressed the luciferase activity of Mmp3, Mmp10, and Mmp13, respectively, in luciferase wild-type reporter constructs. [score:3]
Figure 3B shows that addition of in vitro transcribed miR-128, miR-134, and miR-330 mimics significantly suppressed the luciferase activity of the Mmp3, Mmp10, and Mmp13 3′-UTR upon cotransfection with the luciferase vector (wild-type, mutant, or blank control) with the in vitro transcribed miRNA (miR-128, miR-134, miR-330, or control) mimics into human embryonic kidney (HEK293) cells. [score:3]
The functions of these miRNAs were assessed by transfecting the cells with miR-128, miR-134, and miR-330 mimics (or the corresponding chemically synthesized miRNA inhibitors). [score:3]
MiR-128, miR-134, and miR-330 suppress the tumorigenicity of murine colon cancer cells in vitro and in vivo. [score:3]
Furthermore, the expression levels of miR-128, miR-134, and miR-330 correlated negatively with those of Mmp3, Mmp10, and Mmp13, respectively, in a macrophage mo del of inflammation (r = –0.578, r = –0.65, r = –0.668, respectively; Figure 2E). [score:3]
WT and found that the miR-128, miR-134, and miR-330 mimics reduced the levels of Mmp3, Mmp10, and Mmp13 mRNAs, respectively, whereas each of the inhibitors increased Mmp3, Mmp10, and Mmp13 levels, respectively (Figure 2C). [score:3]
Further, immunohistochemical staining revealed that transfection with the miR-128, miR-134, or miR-330 mimic resulted in decreased expression of Mmp3, Mmp10, or Mmp13, respectively, within tumors (Figure 6E). [score:3]
miR-128, miR-134, and miR-330 suppress the metastasis of murine colon cancer cells in a nude mouse xenograft mo del. [score:3]
MiR-128, miR-134, and miR-330 overexpression in murine colon cancer cells attenuated the ability of the cells to proliferate, migrate, and invade other tissues. [score:3]
When compared with normal colonic tissues, there was a significantly decreased expression of miR-128, miR-134, and miR-330 detected in the colorectal cancer specimens (Supplemental Figure 1B, right). [score:2]
In the present study, we identified miR-128, miR-134, and miR-330 as negative regulators of Mmp3, Mmp10, and Mmp13, respectively. [score:2]
WT cells overexpressing miR-128, miR-134, or miR-330 when compared with that of the control group cells. [score:2]
MiR-128, miR-134, and miR-330 have been reported to play substantive roles in regulating cell proliferation, survival, motility, apoptosis, and invasion [31– 35]. [score:2]
We thus assessed the intracellular levels of Dicer1 and Drosha in RAW264.7 macrophages to verify whether their dysregulation played a role in the observed decrease in miR-128, miR-134, and miR-330 levels during CAC progression. [score:2]
In addition, we assayed the expression levels of miR-128, miR-134, and miR-330 in human colorectal cancer and normal colonic tissues. [score:2]
Moreover, nude mice injected with cells overexpressing miR-128, miR-134, or miR-330 mimic had significantly fewer macroscopic lung metastases compared with the mimic controls (Figure 6D). [score:2]
There was perfect base pairing between the seed sequence of mature miR-128/miR-134/miR-330 and the 3′-UTR of Mmp3/Mmp10/Mmp13 mRNAs, respectively. [score:1]
WT cells that had been transfected with miR-128, miR-134, and miR-330 mimics (or mimics control) were injected into the tail vein of nude mice. [score:1]
To assess the effect of each miRNA (miR-128, miR-134, miR-330) on tumor metastasis, CT26. [score:1]
Thus we tested the effect of miR-128, miR-134, and miR-330 on the metastasis-related aspects in murine colon cancer cells. [score:1]
WT cells transfected with the miR-128, miR-134, and miR-330 mimics or mimics control. [score:1]
As shown in Figure 3A, two miR-128 -binding sites were identified in the 3′-UTR of Mmp3 mRNA, and likewise one miR-134 -binding site was identified for Mmp10 mRNA and one miR-330 -binding site was identified for Mmp13 mRNA. [score:1]
revealed that miR-128, miR-134, and miR-330 decreased the levels of Mmp3, Mmp10, and Mmp13, respectively (Figure 2D). [score:1]
Cells that had been transfected with an miR-128, miR-134, or miR-330 mimic or control mimic were injected into the tail vein of nude mice, and the efficiency of transfection was verified (Figure 6A). [score:1]
WT) transfected with miR-128, miR-134, or miR-330 mimics or mimics control. [score:1]
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[+] score: 110
Deletion of Dicer causes abnormal higher levels of Dcx expression and miRNA-128 over -expression can down-regulate Dcx levels in differentiating adult neural progenitors. [score:8]
Western blot showing the Dcx (arrow) and Actin (loading control) protein levels in (from far right to left): mock (control transfection without miRNA-128-RFP expressing plasmid), miRNA-128 (cells treated with miRNA-128-RFP expressing plasmid), shRNA–Dcx (cells treated with shRNA targeting Dcx) and shRNA-Ctr (cells treated with control shRNA). [score:7]
This indicates that the vector is able to increase the miR-128 levels leading to Dcx down-regulation by translational repression as it has been described for many miRNAs [36]. [score:6]
Both these miRNA are, similarly to miR-128, expressed in the neurogenic areas of the adult mouse brain [35] making them possible additional regulators of Dcx expression. [score:6]
Our results show that miR-128 overexpression reduces the levels of Dcx in differentiating NPCs indicating that miR-128 can target and potentially take part in the regulation of Dcx levels in adult neurogenesis. [score:6]
Indeed miR-128 maintains similar level of expression also in differentiating NPCs (Additional file 2: Fig. S2) when Dcx is physiologically expressed (Fig.   1c). [score:5]
a– c The samples analyzed were mock -treated Neuro2A cells (control transfection without miRNA-128-RFP expressing plasmid) or Neuro2A cells treated with miRNA-128-RFP expressing plasmid. [score:5]
Notably miR128 lacks this complementarity (nucleotides 9–11) in Dcx target sites predicted by the miRNA algorithms TargetScan and microRNA. [score:5]
In agreement with this prediction we found only the Dcx protein but not the transcript being down regulated upon miR128 overexpression (Fig.   3). [score:4]
Dcx KD = Dcx knockdown; miR-128 OE = mirR-128 over -expression; MW = Molecular weight marker. [score:4]
We next asked whether miR-128 could target and regulate Dcx levels in adult NPCs. [score:4]
NS not significant; p = 0.4 Fig.  4Overexpression of miRNA128 reduces Dcx protein levels in “in vitro” differentiating adult neural stem cells. [score:3]
Fig.  3Overexpression of miRNA128 reduces Dcx protein levels in N2A cells. [score:3]
To this purpose we created a miR128-RFP expression vector (see “”). [score:3]
miR128 over -expression reduces Dcx protein in N2 cells. [score:3]
Interestingly, we found a significant decrease in the fraction of Dcx positive cells among the transfected cells when miR-128 is overexpressed (Fig.   4b). [score:3]
Of these, we found only miR-128 to be expressed in adult mouse NPCs (Additional file 2: Fig. S2) in agreement with a previous report [35] showing the presence of miR-128 but not miR-134 in the neurogenic areas of the mouse adult brain. [score:3]
Like many miRNAs, miR-128 has been show to have relatively modest effects on its targets [43]. [score:3]
In line with this view we show that overexpression of the miR-128 in differentiating adult NPCs causes the reduction of the Dcx levels (Fig.   4). [score:3]
b Western blot showing the Dcx and Gapdh (loading control) protein levels in mock and miRNA-128 over -expressing cells. [score:3]
miRNA-128 overexpression. [score:3]
Overexpression of miRNA-128 reduces Doublecortin levels in differentiating adult neural stem cells. [score:3]
RNAi Dicer Argonaute Doublecortin miRNA-128 Adult neurogenesis The precise regulation of proliferation, survival, migration and differentiation of neural stem cells (NSCs) and neural progenitors is crucial for proper formation of the mammalian brain during embryonic, postnatal and adult stages [1– 5]. [score:2]
org) identifies, in addition to miR-128, let-7 and miR-29 as potential regulators of Dcx. [score:2]
Specifically, miR-134 [33] was shown to regulate Dcx in mouse embryonic brain tissues, while miR-128 [34] was found to modulate Dcx levels in a human neuroblastoma cell line. [score:2]
However miR-128 and Dcx are not mutually exclusive in our in vitro cultured NPCs. [score:1]
Cells were seeded on Matrigel-coated 24-well plates (BD Bioscience) at the density of 1.5 × 10e5 cells per well and transfected 24 h later with a miRNA-128-RFP plasmid or a control miRNA-Ctr-RFP plasmid using Lipofectamine 2000 (Life Technologies; ratio DNA/lipofectamine 1:4). [score:1]
The IDs of the TaqMan Probe used were: miR-125 (000449); let-7c (000379); miR-134 (001186); miR-128 (002216); snoRNA55 (001228); snoRNA135 (001230). [score:1]
a Taqman quantitative RT-PCR of the mature miRNA-128 transcripts normalized against the housekeeping small non-coding RNA snoRNA55. [score:1]
Thus, in differentiating NPCs, miR-128 is likely responsible to fine-tune rather than switching off Dcx, by repressing but without eliminating it. [score:1]
Cells were seeded on 6-well plates and after 24 h transfected with or without miRNA-128-RFP plasmid using Lipofectamine 2000 (Life Technologies; ratio DNA/lipofectamine 1:4). [score:1]
To check its functionality we transfected this vector into Neuro2A cells, which resulted in a marked increase in miR-128 levels (Fig.   3a) along with decreased levels of Dcx protein but not the transcript (Fig.   3b, c; Additional file 3: Fig. S3). [score:1]
We then transfected the miR-128-RFP or miR-Ctr-RFP (negative control containing a scrambled miRNA sequence) in adult NPCs (derived from the SVZ of 8-weeks old mice) and let them differentiate for 6 days. [score:1]
The band corresponding to Dcx is reduced in both shRNA–Dcx and miR-128 samples. [score:1]
miRNA128 Rew: 5′-CCT GTCA CAG TGA AGG TCT CTT TGT CAG TCA GTG GCC AAAAC aaa gag acc ggt tca ctg tgaC-3′ (in lower case is the mature miRNA128 sequence). [score:1]
miRNA-128 levels in adult neural progenitors cells. [score:1]
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[+] score: 104
Figure 5 The loss of the retinoblastoma tumor suppressor (RB ) expression plays a role in Smurf2 downregulation in triple -negative breast cancer (TNBC) cells, via upregulation of miR-15, miR-16 and miR-128. [score:11]
We also have revealed that microRNAs such as miR-15a, miR-15b, miR-16 and miR-128, whose expression is increased by inactivating mutations of the retinoblastoma (RB) gene, downregulate translation of Smurf2 protein in TNBC cells. [score:9]
Studies using quantitative PCR and specific microRNA inhibitors indicated that increased expression of miR-15a, miR-15b, miR-16 and miR-128 was involved in Smurf2 downregulation in those triple -negative cancer cell lines, which have mutations in the retinoblastoma (RB) gene. [score:9]
Therefore, RB inactivation accounts at least partly for Smurf2 downregulation in the TNBC cells, via deregulated expression of the miR-15 family and miR-128. [score:7]
miRNAs such as miR-15/16 and miR-128, whose upregulation is linked to the inactivation of RB, play important roles in the downregulation of Smurf2. [score:7]
Therefore, we hypothesized that RB inactivation could result in elevated expression of the miR-15 family and possibly miR-128, which contributed to the downregulation of Smurf2. [score:6]
Low expression of Smurf2 protein was also observed in several TNBC cell lines, which had RB mutations and high expression of miR-15a, miR-15b, miR-16 and miR-128. [score:6]
To further delineate the role of the miRNAs in Smurf2 downregulation observed in BT549, MDA-MB-436 and DU4475 cells, cells were transfected with miRNA inhibitors (antagomirs) against miR-15a, miR-15b, miR-16 or miR-128 (Figure  4). [score:6]
miR-128 is known to target Bmi1, the polycomb transcription factor required for stemness [15, 22], and miR-128 expression may be increased during the transition from the cancer-initiating cell state to the expansive state of breast cancer. [score:5]
DU4475 cells showed increased expression of miR-15b, miR-16 and miR-128, relative to their expression in MCF-10A cells. [score:5]
miR-15/16 and miR-128 mediate Smurf2 downregulation. [score:4]
Figure 4 MicroRNAs such as miR-15, miR-16 and miR-128 are involved in downregulation of Smurf2 protein in triple -negative breast cancer. [score:4]
Interestingly, oncogenic p53(R175H) mutant induces the transcription of miR-128, which then promotes chemoresistance of non-small cell lung cancer [23], presenting another example of high miR-128 expression associated with malignant phenotypes. [score:3]
Cells were transfected with Ambion® Anti-miR™ miRNA Inhibitors specifically against miR-15a, miR-15b, miR-16 and miR-128 (Ambion/Invitrogen, Carlsbad, CA), using the Lipofectamine® RNAiMAX transfection reagent (Invitrogen, Carlsbad, CA) according to the manufacturer’s protocol. [score:3]
Also in MCF-7 cells, the levels of miR-15a, miR-15b and miR16 were low, whereas the expression of miR-128 was modestly higher. [score:3]
High expression of miR-128 has been associated with poor prognosis of ER + breast cancer [21]. [score:3]
Human triple -negative breast cancer cell lines, BT549, MDA-MB-436 and DU4475 cells, were transfected with microRNA inhibitors against miR-15a, miR-15b, miR-16 and miR-128, or nonspecific ssRNA as negative control (NC), and cellular levels of Smurf2 protein were determined at 24 h (A, B) or 48 h (C) post-transfection by immunoblotting. [score:3]
Figure 3 Expression levels of miR-15a, miR-15b, miR-16 and miR-128 in breast cancer cell lines. [score:3]
MDA-MB-436 cells had increased expression of miR-15b, miR-16, and miR-128. [score:3]
The miR-15 family and miR-128 have been implicated for the regulatory network in breast cancer initiating cells [14, 15]. [score:2]
Our finding that miR-15/16 and miR-128 are involved in provides a new pathway to the miRNA -mediated biological processes in breast cancer. [score:1]
The analysis led us to candidates such as miR-128 (binding to Smurf2 3′UTR, 5′-CACUGUGA-3′) and the miR-15 family miRNAs including miR-15a, miR-15b and miR-16 (binding to Smurf2 3′UTR, 5′-GCUGCUA-3′). [score:1]
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[+] score: 48
T1 expression is up-regulated whereas miR-128 expression is down-regulated in the spinal cord of ALS G93A mice and in human SALS. [score:11]
T1 up-regulation associated with down-regulation of miR-128 and disease progression in human sporadic ALS and in an ALS animal mo del, we suggest that TrkC. [score:9]
T1 up-regulation in spinal cord astrocytes in a mouse ALS mo del and human sporadic ALS is due to miR128 downregulation. [score:7]
Data are expressed as the mean + SEM (n = 8 spinal cord samples each group (B) The levels of miR-128 (regulator of TrkC. [score:4]
T1 is up-regulated in mouse and human ALS, due to decreased miR-128, a miR that destabilizes TrkC. [score:4]
1 [TrkC-T1] vectors, or by re -expressing miR-128 to promote degradation of TrkC. [score:3]
In healthy wild type spinal cord miR128 is expressed. [score:3]
T1 mRNA and reduced miR128 are detected in the mutant SOD1 mouse mo del, and also in humans with ALS unrelated to SOD1 mutations (which represent the majority of clinical cases). [score:2]
T1 mRNA and protein, whereas reduced miR128 levels would lead to increased TrkC. [score:1]
Pre-symptomatic ALS spinal cords (~100 days of age) have lower miR128, and symptomatic ALS spinal cords (~140 days of age) have even lower miR128 levels (p<0.003). [score:1]
T1 mRNA is destabilized by micro -RNA miR128 [24]. [score:1]
A miR128-promoted degradation would explain why healthy spinal cords have low or undetectable TrkC. [score:1]
T1 mRNA in human SALS is associated with significantly reduced levels of miR128 (a known disruptor of TrkC. [score:1]
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[+] score: 39
Previously, Mao et al. reported that miR-128-3p directly targets the MAPK14 3’UTR and downregulates MAPK14 protein expression; furthermore, an increased miR-128-3plevel was found to contribute to neuronal survival in an ischemia -induced brain injury [33]. [score:9]
MiR-449a-3p, miR-298-5p, miR-92a-1-5p, miR-423-5p, miR-423-3p, miR-128-3p and miR-340-3p were found to be significantly downregulated (A-G, all p < 0.05), and miR-21a-3p was found to be significantly upregulated at 6 hours after heat treatment (J, p = 0.006). [score:7]
Seven of these miRNAs were found to be significantly downregulated (miR-449a-3p, miR-298-5p, miR-92a-1-5p, miR-423-5p, miR-423-3p, miR-128-3p, miR-340-3p), and 1 was found to be significantly upregulated (miR-21a-3p) at 6 hours after transient scrotal heat treatment. [score:7]
Similarly, our report is the first to describe the significant downregulation of miR-128-3p expression in the testis after scrotal hyperthermia. [score:6]
Furthermore, the heat -induced downregulation of miR-128-3p may promote germ cell apoptosis by up -regulating MAPK14, which was supported by finding of a significantly negative association between relative miR-128-3p level and the germ cell AI in a correlation analysis (r = -0.48, p = 0.033). [score:5]
Finally, some of the identified miRNAs (e. g., miR-449a-3p, miR-92a-1-5p, miR-423-3p, and miR-128-3p) correlated closely with germ cell apoptosis. [score:1]
We found that the relative levels of miR-449a-3p, miR-92a-1-5p, miR-423-3p and miR-128-3p correlated significantly and negatively with the germ cell AI (r = -0.58, -0.58, -0.45, and -0.48, respectively; p = 0.007, 0.007, 0.045, and 0.033, respectively). [score:1]
Collectively, these findings suggest a critical role for miR-128-3p in maintaining normal spermatogenesis. [score:1]
Figure 7The relative levels of miR-449a-3p (A), miR-92a-1-5p (C), miR-423-3p (E) and miR-128-3p (F) correlated significantly and negatively with the germ cell AI (r = -0.58, -0.58, -0.45, and -0.48, respectively; p = 0.007, 0.007, 0.045, and 0.033, respectively); the relative level of miR-21a-3p (H) correlated significantly and positively with the AI (r = 0.56, p = 0.01). [score:1]
The relative levels of miR-449a-3p (A), miR-92a-1-5p (C), miR-423-3p (E) and miR-128-3p (F) correlated significantly and negatively with the germ cell AI (r = -0.58, -0.58, -0.45, and -0.48, respectively; p = 0.007, 0.007, 0.045, and 0.033, respectively); the relative level of miR-21a-3p (H) correlated significantly and positively with the AI (r = 0.56, p = 0.01). [score:1]
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[+] score: 38
Among the 4 differentially expressed miRNAs of this study, miR-128 is a brain enriched miRNA which is highly expressed during neuronal differentiation [42]. [score:5]
Moreover, it was demonstrated that miR-128 down-regulated genes involved in insulin signaling (e. g. ; insulin receptor, insulin receptor substrate-1 and phosphatidylinositol 3-kinases regulatory 1) in muscle cells [39]. [score:5]
Interestingly, miR-128 which was positively correlated with cholesterol level in our Indian population and in the diabetic mice, has been shown to post-transcriptionally inhibit the cholesterol transporters and play a regulatory role in cholesterol efflux and cholesterol homeotasis [38]. [score:4]
For example, the expression of miR-128, which was stronly correlated with the level of cholesterol, was significantly more increased in the serum of pre- and diabetic women and in men. [score:3]
Statistical data analysis revealed that the mean expression level of 9 miRNAs (i. e. ; miR-128, miR-99b-5p, miR-130b-3p, miR-142-3p, miR-374a-5p, miR-423-5p, miR-484, miR-629-5p, let-7d-3p) was significantly different (student t-test p<0.05) across the studied groups (Table 2). [score:3]
Altered expressions of miR-128 in pre-diabetic state vs control was found significant in the group of women only. [score:3]
In addition, the group of diabetic men was significantly younger than the group of diabetic women (41.7 ± 1.45 vs 47.08 ± 1.72; p = 0.02) which could explain that some miRNAs differentially expressed between controls and diabetics were not significantly altered in the group of men (i. e. ; miR-128; miR-374a, miR-142-3p and let-7d-3p). [score:3]
In the context of the well-known insulin-resistance effects, high-fat diet led to increased circulating concentrations of miR-128, miR-130b-3p, miR-99b-5p, miR-629a-5p and miR-let-7d-3p expression in HFD mice compared with NPD fed mice (p<0.05). [score:2]
Considering the whole population, this analysis revealed 4 differentially expressed miRNAs (miR-128, miR-130b-3p, miR-374a-5p, miR-423-5p) in subjects with prediabetes and T2DM patients compared to control subjects with normal glucose tolerance. [score:2]
Taking into consideration of all these data, we suggested that the increased level of circulating miR-128 might be linked to the development of dyslipedemia associated with T2DM. [score:2]
As shown on Fig 1, altered expressions of miR-128 and miR-423-5p in pre-diabetic patients compared to controls were confirmed with high significance (p<0.05). [score:2]
Among the altered circulating miRNAs identified in this study, miR-128 has never been described in previous studies [26– 33, 37]. [score:1]
Interestingly, miR-128 has been shown to be one of the circulatory miRNA biomarkers for detection of mild cognitive impairment [44]. [score:1]
Our study also highlighted that some miRNAs (miR-128 and miR-374a, miR-142-3p, let-7d-3p, miR-423-5p) had sex-specific associations with prediabetes or diabetes. [score:1]
2015. doi: 10.1007/s00125-015-3510-2 38 Adlakha YK, Saini N. miR-128 exerts pro-apoptotic effect in a p53 transcription -dependent and-independent manner via PUMA-Bak axis. [score:1]
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10
[+] score: 33
Of the ten miRNAs downregulated in Ercc1 [−/−] MEFs, eight (miR-449a, miR-455*, miR-128, miR-497, miR-543, miR-450b-3p, miR-872 and miR-10b) were also down-regulated in both the progeroid and old WT mouse livers compared to the WT young (20 week) control mouse livers (Figure 1). [score:6]
Of the 8 downregulated miRNAs in Ercc1 [−/Δ] and WT old mouse liver compared to WT young mouse liver (Figure 1), three miRNAs (miR-449a, miR-455*, miR-128) were also downregulated in the kidneys of progeroid mice compared to WT young mice (Figure 2). [score:5]
Three miRNAs (miR-128, miR-449a and miR-455*) are downregulated in late passage MEFs as well as liver and kidney tissues of both progeroid Ercc1 [−/Δ] and WT old mice. [score:4]
Three of these miRNAs (miR-128, miR-449a and miR-455*) were also downregulated in the kidneys of progeroid and WT old mouse compared to the young WT mouse kidneys (Figure 2). [score:3]
Eight miRNAs (miR-449a, miR-455*, miR-128, miR-497, miR-543, miR-450b-3p, miR-872 and miR-10b) are significantly downregulated in the livers of progeroid Ercc1 [−/Δ] and naturally aged mice compared to young adult mice (Figure 1). [score:3]
Additionally, we demonstrate that several miRNAs differentially expressed in the Ercc1 [−/−] MEFs (miR-449a, miR-455*, miR-128, miR-497, miR-543, miR-450b-3p, miR-872 and miR-10b) were also dysregulated in liver tissues of both progeroid Ercc1 [−/Δ] and old WT mice compared to young WT mice. [score:3]
Previously confirmed gene targets of the miRNAs identified in this study that are linked to cellular senescence and aging (miR-449a, miR-455*, miR-128, miR-497, miR-543, miR-450b-3p, miR-872 and miR-10b) are listed in Supplemental Table S1. [score:3]
We show that three of the above miRNAs (miR-449a, miR-455* and miR-128) were downregulated in kidney tissues from Ercc1 [−/Δ]progeroid and WT old mice compared to the young mice. [score:3]
In summary, we identified several miRNAs that are similarly dysregulated in senescent primary MEFs and senescent tissues of progeroid and naturally aged mice (miR-449a, miR-455*, miR-128, miR-497, miR-543, miR-450b-3p, miR-872 and miR-10b). [score:2]
We analyzed the levels of 13 miRNAs confirmed to be dysregulated in P7 Ercc1 [−/−] MEFs compared to P3 Ercc1 [−/−] MEFs (miR-680, miR-320, miR-22, miR-449a, miR-455*, miR-675-3p, miR-128, miR-497, miR-543, miR-450b-3p, miR-872, miR-369-5p and miR-10b) in RNA samples prepared from the livers of WT young (20 weeks), the progeroid Ercc1 [−/Δ] mice, and WT old mice (30 months). [score:1]
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[+] score: 33
In four independent differentiation procedures we could confirm the microarray data (Fig. 5A)–that is, a strong concentration -dependent induction of muscle-specific/abundant miRNA (mir-206, mir-10a, mir-214, mir-145, mir-143, mir-199a) and a significant downregulation of the expression of neuro-specific miRNAs (mir-124, mir-128, mir-137, mir-491, mir-383) in comparison to the solvent control. [score:6]
Mir-128 and mir-137 were downregulated, while mir-124 was not. [score:4]
Myogenesis regulating mir-206 is highly expressed in skeletal muscles in both species [62], [63] as is mir-124, mir-9, mir-128 and mir-137 in mouse and human brain where they are responsible for fine-tuning of neurogenesis [62] [64]. [score:4]
From two primary mir-128 transcripts only pri -mir128-1 was detectable and slightly downregulated in our cell system. [score:4]
miRNAs involved in embryonic and adult neurogenesis such as mir-137, mir-128, mir-124a, mir-326, or mir-7 were found significantly downregulated by VPA. [score:4]
mir-9 was strongly induced from day 9 of differentiation onwards, while mir-124 and mir-128 were induced later on reaching their maximum expression levels both on day 16 ([47] and Fig. S1F). [score:3]
For the same reason we did not observe any differences in the expression of neuron-specific miRNA in primary cultures (mir-124, mir-128, Fig. S3), which are known to play a significant role in earlier, but not later stages, of neurogenesis. [score:3]
These results suggest that VPA affects neural differentiation processes and pathways, which are specific for mir-124 but not mir-9. Exposure of differentiating mESCs to VPA also reduced expression of mir-128, which is an enhancer of neural differentiation [88]. [score:3]
Most regulated miRNAs shown in our study are highly conserved between mice and humans (e. g. mir-206, mir-214, mir-10a, mir-124, mir-137, mir-128, mir-9) [61], [62]. [score:2]
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12
[+] score: 27
miR-124 precursor expression was not different between SCZ and control individuals and the differentially expressed miR-137 target genes may only slightly be co-regulated by miR-124 and miR-128. [score:8]
miR-137 acts cooperatively and synergistically with miR-124 and miR-128 [7, 33, 34]; therefore, changes in the expression of these two microRNAs may interfere with the expression of miR-137 target genes. [score:7]
We analyzed miR-124 and miR-128, which act cooperatively with miR-137, and obtained no evidence that these two microRNAs influence the differential expression of miR-137 targets. [score:5]
Several targets listed in Table  1 had putative binding sites for miR-124 (5 out of 16) and miR-128 (1 out of 16) (Additional file  1: Table S7). [score:3]
Analysis of the 3′UTR of the differentially expressed miR-137 genes in the DLPFC between SCZ and control individuals for additional putative miR-124 and miR-128 binding sites. [score:3]
No data was available for MIR-128 (ENSG00000207654, ENSG00000207625) or for mature microRNAs. [score:1]
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13
[+] score: 25
Within the 3′ UTR of Prdm16, there are putative target sites for miR-1, miR-206, miR-133a and miR-128 (Fig. 1C), raising the possibility that these miRNAs target Prdm16 mRNA. [score:5]
Plasmids carrying firefly luciferase gene linked to fragments of Prdm16-3′UTRs harboring the putative target sites of miR-206, miR-1, or miR-128 were co -transfected to HEK293 cells along with control miRNA, miR-206 mimic, miR-1 mimic, or miR-128 mimic (Invitrogen). [score:3]
These results suggest that miR-133a and miR-128 targets the 3′ UTR of Prdm16. [score:3]
Consistently, miR-133a but not miR-128 was significantly downregulated in the differentiated mature adipocytes compared to APC (Fig. 2F). [score:3]
Notably, qPCR results demonstrate that miR-133a is decreased by 80%, but miR-128 is not significantly altered, in the mG [+] cells (Fig. 2D), suggesting that miR-133a is more likely to target Prdm16 in vivo. [score:3]
miR-133a and miR-128 target the 3′ UTR of Prdm16 in HEK293 cells. [score:3]
Interestingly, we identified four miRNAs (miR-1, miR-206, miR-133a and miR-128) that are expressed at significantly lower levels in the ingWAT compared to the asWAT (Fig. 1B, Fig. S1). [score:2]
Plasmids carrying luciferase gene linked to 3′ UTR of Prdm16 were cotransfected to HEK293 cells, along with control miRNA, miR-133a (D) or miR-128 (E) at indicated doses. [score:1]
1003626.g001 Figure 1(A–B) qPCR analysis of miR-1, miR-206, miR-133a, miR-128 and Prdm16, for asWAT and ingWAT of wildtype mice. [score:1]
miR-128 also repressed the luciferase activity by ∼50% at 10–100 nM (Fig. 1E). [score:1]
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14
[+] score: 18
Other miRNAs from this paper: hsa-let-7a-1, hsa-let-7a-2, hsa-let-7a-3, hsa-let-7b, hsa-let-7c, hsa-let-7d, hsa-let-7e, hsa-let-7f-1, hsa-let-7f-2, hsa-mir-17, hsa-mir-18a, hsa-mir-19b-1, hsa-mir-19b-2, hsa-mir-21, hsa-mir-23a, hsa-mir-31, hsa-mir-92a-1, hsa-mir-92a-2, hsa-mir-96, hsa-mir-98, hsa-mir-99a, hsa-mir-106a, mmu-let-7g, mmu-let-7i, mmu-mir-23b, mmu-mir-99a, mmu-mir-127, mmu-mir-128-1, mmu-mir-136, mmu-mir-142a, mmu-mir-145a, mmu-mir-10b, mmu-mir-182, mmu-mir-183, mmu-mir-187, mmu-mir-193a, mmu-mir-195a, mmu-mir-200b, mmu-mir-206, mmu-mir-143, hsa-mir-139, hsa-mir-10b, hsa-mir-182, hsa-mir-183, hsa-mir-187, hsa-mir-210, hsa-mir-216a, hsa-mir-217, hsa-mir-219a-1, hsa-mir-221, hsa-mir-222, hsa-mir-224, hsa-mir-200b, mmu-mir-302a, mmu-let-7d, mmu-mir-106a, hsa-let-7g, hsa-let-7i, hsa-mir-23b, hsa-mir-128-1, hsa-mir-142, hsa-mir-143, hsa-mir-145, hsa-mir-127, hsa-mir-136, hsa-mir-193a, hsa-mir-195, hsa-mir-206, mmu-mir-19b-2, mmu-mir-200a, mmu-let-7a-1, mmu-let-7a-2, mmu-let-7b, mmu-let-7c-1, mmu-let-7c-2, mmu-let-7e, mmu-let-7f-1, mmu-let-7f-2, mmu-mir-18a, mmu-mir-21a, mmu-mir-23a, mmu-mir-31, mmu-mir-92a-2, mmu-mir-96, mmu-mir-98, hsa-mir-200c, mmu-mir-17, mmu-mir-139, mmu-mir-200c, mmu-mir-210, mmu-mir-216a, mmu-mir-219a-1, mmu-mir-221, mmu-mir-222, mmu-mir-224, mmu-mir-19b-1, mmu-mir-92a-1, hsa-mir-128-2, mmu-mir-217, hsa-mir-200a, hsa-mir-302a, hsa-mir-219a-2, mmu-mir-219a-2, hsa-mir-363, mmu-mir-363, hsa-mir-302b, hsa-mir-302c, hsa-mir-302d, hsa-mir-371a, hsa-mir-18b, hsa-mir-20b, hsa-mir-452, mmu-mir-452, ssc-mir-106a, ssc-mir-145, ssc-mir-216-1, ssc-mir-217-1, ssc-mir-224, ssc-mir-23a, ssc-mir-183, ssc-let-7c, ssc-let-7f-1, ssc-let-7i, ssc-mir-128-1, ssc-mir-136, ssc-mir-139, ssc-mir-18a, ssc-mir-21, hsa-mir-146b, hsa-mir-493, hsa-mir-495, hsa-mir-497, hsa-mir-505, mmu-mir-20b, hsa-mir-92b, mmu-mir-302b, mmu-mir-302c, mmu-mir-302d, hsa-mir-671, mmu-mir-216b, mmu-mir-671, mmu-mir-497a, mmu-mir-495, mmu-mir-146b, mmu-mir-708, mmu-mir-505, mmu-mir-18b, mmu-mir-493, mmu-mir-92b, hsa-mir-708, hsa-mir-216b, hsa-mir-935, hsa-mir-302e, hsa-mir-302f, ssc-mir-17, ssc-mir-210, ssc-mir-221, mmu-mir-1839, ssc-mir-146b, ssc-mir-206, ssc-let-7a-1, ssc-let-7e, ssc-let-7g, ssc-mir-128-2, ssc-mir-143, ssc-mir-10b, ssc-mir-23b, ssc-mir-193a, ssc-mir-99a, ssc-mir-98, ssc-mir-92a-2, ssc-mir-92a-1, ssc-mir-92b, ssc-mir-142, ssc-mir-497, ssc-mir-195, ssc-mir-127, ssc-mir-222, ssc-mir-708, ssc-mir-935, ssc-mir-19b-2, ssc-mir-19b-1, ssc-mir-1839, ssc-mir-505, ssc-mir-363-1, hsa-mir-219b, hsa-mir-371b, ssc-let-7a-2, ssc-mir-18b, ssc-mir-187, ssc-mir-218b, ssc-mir-219a, mmu-mir-195b, mmu-mir-145b, mmu-mir-21b, mmu-let-7j, mmu-mir-21c, ssc-let-7d, ssc-let-7f-2, ssc-mir-20b-1, ssc-mir-20b-2, ssc-mir-31, ssc-mir-182, ssc-mir-216-2, ssc-mir-217-2, ssc-mir-363-2, ssc-mir-452, ssc-mir-493, ssc-mir-671, mmu-let-7k, ssc-mir-7138, mmu-mir-219b, mmu-mir-216c, mmu-mir-142b, mmu-mir-497b, mmu-mir-935, ssc-mir-9843, ssc-mir-371, ssc-mir-219b, ssc-mir-96, ssc-mir-200b
adj ssc-miR-371-5p 11.3640 6.94E-19 7.93E-18 ssc-miR-219b-3p 10.1953 2.42E-32 1.94E-30 ssc-miR-218b 5.3242 5.95E-18 5.95E-17 ssc-miR-92b-3p 3.2034 3.39E-17 3.01E-16 ssc-miR-7138-3p 2.0714 1.31E-02 1.59E-02 ssc-miR-219a 2.0675 1.31E-07 4.37E-07 ssc-miR-99a 1.4504 2.83E-06 8.09E-06 ssc-miR-128 1.1854 1.31E-05 3.49E-05 To validate this differential miRNA expression pattern, we performed quantitative stem-loop RT-PCR to assess the expression of the three[35] selected hpiPSCs- specific miRNAs: ssc-miR-371-5p, ssc-miR-106a and ssc-miR-363, which were found to be more highly expressed in hpiPSCs (Fig 3B). [score:7]
adj ssc-miR-371-5p 11.3640 6.94E-19 7.93E-18 ssc-miR-219b-3p 10.1953 2.42E-32 1.94E-30 ssc-miR-218b 5.3242 5.95E-18 5.95E-17 ssc-miR-92b-3p 3.2034 3.39E-17 3.01E-16 ssc-miR-7138-3p 2.0714 1.31E-02 1.59E-02 ssc-miR-219a 2.0675 1.31E-07 4.37E-07 ssc-miR-99a 1.4504 2.83E-06 8.09E-06 ssc-miR-128 1.1854 1.31E-05 3.49E-05To validate this differential miRNA expression pattern, we performed quantitative stem-loop RT-PCR to assess the expression of the three[35] selected hpiPSCs- specific miRNAs: ssc-miR-371-5p, ssc-miR-106a and ssc-miR-363, which were found to be more highly expressed in hpiPSCs (Fig 3B). [score:7]
Cell cycle and Neurotrophin signaling pathway were regulated by ssc-miR-20b, ssc-miR-128, ssc-miR-497, ssc-miR-195 and ssc-miR-371-5p through corresponding putative target genes. [score:4]
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15
[+] score: 18
We have previously shown SNAP25 to be down regulated in scrapie infected mice, potentially targeted by the up-regulated miR-128. [score:7]
Expression of SNAP25 has recently been shown to be down-regulated by miR-128 leading to perturbation of neuronal activity [36]. [score:6]
Of these, only miR-128 was significantly up-regulated in the brains of scrapie infected mice. [score:4]
Only a small number of miRNAs have so far been associated with neurodegenerative processes: miR-133b, miR-9, miR-125b, miR-132, miR-124a, miR-219 and miR-128 [19], [20], [47]. [score:1]
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16
[+] score: 17
We also found that predicted targets of miR-128 were significantly down-regulated in the neurons of the auditory and vestibular systems, while the predicted targets of miR-9 were significantly down-regulated only in the neurons of the auditory system. [score:11]
The strength of this approach is further demonstrated by the ability to detect not only compartment specific regulators of cell fate (Zeb1/2, c-Ets1/2, miR-128, miR-9 and miR200b) but also miR-96, a miRNA which is expressed only in a subset of the sensory epithelial cells. [score:4]
Both miR-128 and miR-9 are known to have an important function in neuronal development [16]. [score:2]
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17
[+] score: 17
Down-regulation of miR-128 expression has been associated with glioblastoma multiforme [48] whereas its up-regulation has been implicated with reduced neuroblastoma cell motility, invasiveness and cell growth [49]. [score:9]
In addition, both miR-128 and miR-9 are highly expressed in the foetal hippocampus and differentially regulated in the normal adult hippocampus as well as the hippocampus of Alzheimer's disease sufferers [50]. [score:6]
MiR-128 (7,303 CPM) was highly expressed in our dataset and the finding is in agreement with a previous study [47]. [score:2]
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18
[+] score: 16
The expressions of miR-711, miR-714, miR-744, miR-2137, miR-5130, miR-1892, miR-328, miR-346, miR-5099, and miR-705 were significantly upregulated in I/R injured heart grafts, while miR-490, miR-491, miR-210, miR-362, miR-24, miR-423, miR-128, miR-328, miR -181, and miR-532 were downregulated. [score:9]
As compared with cells under normxia, miR-711, miR-714, miR-328, miR-346, miR-210, miR-744, miR-5130, miR-181a and miR-2137 were significantly over-expressed in hypoxia/reperfusion treated cardiomyocytes, while the expression of miR-491, miR-211, miR-532, miR-185, miR-425, miR-128, miR-24 was down-regulated (Figure 4B). [score:7]
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19
[+] score: 15
Similarly, 342 genes potentially downregulated (targets of mmu-miR-128 and mmu-miR-342-5p) and 200 potentially upregulated genes (targets of mmu-miR-465c-5p, mmu-miR-466d-3p, mmu-miR-466d-5p, mmu-miR-665, mmu-miR-683) in the colon were identified (Table S4). [score:11]
qRT-PCR was performed using SYBR Green qPCR Master Mix (Fermentas) on a Mastercycler Realplex [4] (Eppendorf) using the following primers:For mature miRNA expression: the universal primer provided in the NCode [TM] miRNA first-strand cDNA synthesis kit was used together with one of the following forward primer: mmu-miR-665: 5′-ACCAGG AGG CTG AGG TCC CT-3′mmu-miR-128: 5′-TCACAGTGAACCGGTCTCTTT-3′ mmu-mir-200c*: 5′-CGTCTTACCCAGCAGTGTTTGG-3′ mmu-miR-342-5p: 5′-AGGGGTGCTATCTGTGATTGAG-3′ mmu-miR-466d-3p: 5′-TATACATACACGCACACATAG-3′ mmu-miR-466d-5p: 5′-TGTGTGTGCGTACATGTACATG-3′ mmu-miR-465c-5p: 5′-TATTTAGAATGGCGCTGATCTG-3′ mmu-miR-683: 5′-CCTGCTGTAAGCTGTGTCCTC-3′ mmu-miR-665: 5′-ACCAGGAGGCTGAGGTCCCT-3′ mmu-miR-298: 5′-GGCAGAGGAGGGCTGTTCTTCCC-3′ For Abcc3 expression:Forward 5′-CTT CTT TTC CCG CTT GTC TTT-3′;Reverse 5′- CCT CCT CAG ACA GAG ACC AGA-3′. [score:2]
qRT-PCR was performed using SYBR Green qPCR Master Mix (Fermentas) on a Mastercycler Realplex [4] (Eppendorf) using the following primers: For mature miRNA expression: the universal primer provided in the NCode [TM] miRNA first-strand cDNA synthesis kit was used together with one of the following forward primer: mmu-miR-665: 5′-ACCAGG AGG CTG AGG TCC CT-3′ mmu-miR-128: 5′-TCACAGTGAACCGGTCTCTTT-3′ mmu-mir-200c*: 5′-CGTCTTACCCAGCAGTGTTTGG-3′ mmu-miR-342-5p: 5′-AGGGGTGCTATCTGTGATTGAG-3′ mmu-miR-466d-3p: 5′-TATACATACACGCACACATAG-3′ mmu-miR-466d-5p: 5′-TGTGTGTGCGTACATGTACATG-3′ mmu-miR-465c-5p: 5′-TATTTAGAATGGCGCTGATCTG-3′ mmu-miR-683: 5′-CCTGCTGTAAGCTGTGTCCTC-3′ mmu-miR-665: 5′-ACCAGGAGGCTGAGGTCCCT-3′ mmu-miR-298: 5′-GGCAGAGGAGGGCTGTTCTTCCC-3′ For Abcc3 expression: Forward 5′-CTT CTT TTC CCG CTT GTC TTT-3′; Reverse 5′- CCT CCT CAG ACA GAG ACC AGA-3′. [score:2]
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20
[+] score: 14
Other miRNAs from this paper: mmu-mir-128-1, mmu-mir-130b, mmu-mir-98, mmu-mir-338
Integrins have been shown to be downregulated by microRNAs in several studies in different types of cancer, some of which regulate ITGB3 translation, such as miR-128, which is upregulated in hypoxia [81, 82], miR-98 in hypoxia and miR-338, which inhibits migration by targeting HIF1α under low-oxygen conditions [83]. [score:14]
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21
[+] score: 12
Several microRNAs (Mir128, Mir181d, Mir92b) have been implicated in regulation of neuronal development and differentiation; several of the top mRNA modules enriched in targets of the microRNAs are also enriched in developmental genes. [score:5]
Other examples of strongly negatively correlated microRNA-module pairs with strong enrichment of predicted targets include Mir132 and module M1 (correlation -0.63, enrichment p-value 2×10 [−6]), Mir181d and module M34 (correlation -0.58, enrichment p-value 4×10 [−6]), and Mir128 and module M39 (correlation -0.58, enrichment p-value 1×10 [−7]). [score:3]
Mir128 has been implicated in regulation of motor behavior by modulating neuronal signaling networks and excitability [25] and in regulating cortical lamination as well as for the development of neuronal morphology and intrinsic excitability [26]. [score:3]
These 15 microRNAs include Mir128 (in both -1 and -2 forms) that has been implicated in regulating motor behavior by modulating neuronal signaling networks and excitability in adult neurons [30]; Mir218, Mir369 and Mir543. [score:1]
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22
[+] score: 11
Other miRNAs from this paper: mmu-mir-128-1, mmu-mir-218-1, mmu-mir-218-2
miR-218 and miR-128 down-regulate cathepsin B expression when they are up-regulated in medulloblastoma cell lines (84) and AD monocytes and lymphocytes (85) and are expressed in brain neurons (81, 86). [score:11]
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23
[+] score: 10
Among the miRNAs that were significantly upregulated in SAMP8 compared with SAMR1 mice, miR-30e-5p, miR-125b-5p, and miR-128-3p have also been reported to be upregulated in post-mortem human AD hippocampus (Lukiw, 2007; Cogswell et al., 2008). [score:6]
Notably, our study highlights the upregulation of miR-30e-5p, miR-125b-5p, and miR-128-3p as common epigenetic features in the hippocampus of SAMP8 mice and post-mortem hippocampus from AD patients. [score:4]
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24
[+] score: 10
identified functional, non-canonical regulation globally for miR-128 and miR-124 (Fig. 2), and for individual miR-9, miR-181, miR-30 and miR-125 targets (Fig. 4f and Fig. 8b–m). [score:4]
For brain polyribosome -associated mRNAs from miR-128 knockout (KO) and wild-type (WT) mice, the presence of miR-128 chimeras in transcript 3′-UTRs correlated with enhanced polysome association in miR-128 KO brain (Fig. 2a) 2. Sites with canonical seed matches and non-canonical sites predicted significant de-repression (Fig. 2b). [score:2]
Non-miR-128 3′-UTR chimeras were plotted as controls. [score:1]
Normalized microarray values for CAD neuroblastoma cells transfected with miR-124 or control mimics were obtained from GEO and processed as for miR-128 profiles 38. [score:1]
For cumulative distribution function (CDF) analysis (Fig. 2a,b), log [2]FC ratios (KO/WT) in transcript polysome association were plotted for miR-128 3′-UTR chimera sites. [score:1]
Normalized microarray values for polyribosome profiles in miR-128 KO and WT mouse brains were obtained from GEO 2. Genes with contradictory probe information (different signs) were filtered and probe log [2] fold-change (log [2]FC) values for remaining genes were averaged. [score:1]
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25
[+] score: 9
Also, miR-125a-5p/-351, miR-200c/-429, miR-106b/-17, miR-363/-92b, miR-181b/-181d, miR-19a/-19b, let-7d/-7f, miR-18a/-18b, miR-128/-27b and miR-106a/-291a-3p pairs exhibited significant synergy and their association to aging and/or cardiovascular diseases is supported in many cases by a disease database and previous studies. [score:5]
Further, we comment on miR-27b (miR-128/-27b pair appeared on the 8 [th] rank) which was shown to be up-regulated to different degrees in the old versus young adult heart and was induced during early hypertrophic growth in response to pressure-overload [6]. [score:4]
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26
[+] score: 9
A total of 11 miRNAs, let-7, miR-9, miR-206, miR-138, miR-133, miR-152, miR-137, miR-128, miR-143, miR-27b and miR-218 were co-expressed by 18 synaptic transmission target genes (Table S6). [score:5]
Again, the GO processes were composed of two sub-trees (Figure 3B), as in development, for shared miRNAs, such as miR-9, miR-206, miR-138, miR-133, miR-152, and miR-128. [score:2]
For synaptic transmission, miR-128, miR-27b, miR-133, miR-206, miR-152 and miR-9 are shared between development and tumor using picTar prediction; miR-128, miR-140, miR-27b, miR-22, miR-133, miR-223 and miR-152 are shared using PITA prediction. [score:2]
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27
[+] score: 8
Only 2 deregulated miRNAs overlapped between the brain regions consisting of the miR-128-3p (down-regulated in hippocampus and olfactory bulb) and let-7i-5p (up-regulated in neocortex and olfactory bulb) (Figure 7A and 7B). [score:8]
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28
[+] score: 8
Other miRNAs from this paper: mmu-mir-128-1
Upregulation of miR-128 was shown to target the transcripts of these enzymes and mediate their suppression. [score:8]
[1 to 20 of 1 sentences]
29
[+] score: 8
Apart from global modulation of miRNA biogenesis, mutant p53 also affects expression of miRNAs, principally by downregulating tumor-suppressive miRNAs – miR-130b in endometrial cancer (24), miR-27a in breast cancer cells (MDA-MB-468) (25), miR-223 in breast and colon cells (26), let-7i in breast cancer and DLD1 cells (colorectal cancer) (27), and miR-205 (28), and elevating oncogenic miRNAs: miR-128-2 (29) and miR-155 in breast cancer cells (30) to mediate its oncogenic functions. [score:8]
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30
[+] score: 8
TIFA, with an up-regulated gene transcriptional level (Supplementary Figure S1B), was predicted to be a target gene of miR-409-5p and miR-128-3p; and these miRNAs all showed decreased expression upon MC-LR treatment (Supplementary Table S2). [score:8]
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31
[+] score: 7
Downregulation of miR-7 was previously reported in glioblastoma [24] along with underexpression of miR-128 in lung cancer [23], but in HNSCC cell lines the expression of these miRNAs was variable as compared to controls (Fig. S1A). [score:7]
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32
[+] score: 7
Other miRNAs from this paper: hsa-let-7c, hsa-let-7d, hsa-mir-16-1, hsa-mir-21, hsa-mir-24-1, hsa-mir-24-2, hsa-mir-28, hsa-mir-29a, hsa-mir-30a, hsa-mir-31, hsa-mir-99a, hsa-mir-101-1, hsa-mir-16-2, mmu-let-7g, mmu-let-7i, mmu-mir-27b, mmu-mir-30a, mmu-mir-99a, mmu-mir-101a, mmu-mir-125b-2, mmu-mir-126a, mmu-mir-128-1, mmu-mir-9-2, mmu-mir-142a, mmu-mir-144, mmu-mir-145a, mmu-mir-151, mmu-mir-152, mmu-mir-185, mmu-mir-186, mmu-mir-24-1, mmu-mir-203, mmu-mir-205, hsa-mir-148a, hsa-mir-34a, hsa-mir-203a, hsa-mir-205, hsa-mir-210, hsa-mir-221, mmu-mir-301a, mmu-let-7d, hsa-let-7g, hsa-let-7i, hsa-mir-27b, hsa-mir-125b-1, hsa-mir-128-1, hsa-mir-142, hsa-mir-144, hsa-mir-145, hsa-mir-152, hsa-mir-9-1, hsa-mir-9-2, hsa-mir-9-3, hsa-mir-125b-2, hsa-mir-126, hsa-mir-185, hsa-mir-186, mmu-mir-148a, mmu-mir-200a, mmu-let-7c-1, mmu-let-7c-2, mmu-mir-16-1, mmu-mir-16-2, mmu-mir-21a, mmu-mir-24-2, mmu-mir-29a, mmu-mir-31, mmu-mir-34a, mmu-mir-148b, mmu-mir-339, mmu-mir-101b, mmu-mir-28a, mmu-mir-210, mmu-mir-221, mmu-mir-9-1, mmu-mir-9-3, mmu-mir-125b-1, hsa-mir-128-2, hsa-mir-200a, hsa-mir-101-2, hsa-mir-301a, hsa-mir-151a, hsa-mir-148b, hsa-mir-339, hsa-mir-335, mmu-mir-335, hsa-mir-449a, mmu-mir-449a, hsa-mir-450a-1, mmu-mir-450a-1, hsa-mir-486-1, hsa-mir-146b, hsa-mir-450a-2, hsa-mir-503, mmu-mir-486a, mmu-mir-542, mmu-mir-450a-2, mmu-mir-503, hsa-mir-542, hsa-mir-151b, mmu-mir-301b, mmu-mir-146b, mmu-mir-708, hsa-mir-708, hsa-mir-301b, hsa-mir-1246, hsa-mir-1277, hsa-mir-1307, hsa-mir-2115, mmu-mir-486b, mmu-mir-28c, mmu-mir-101c, mmu-mir-28b, hsa-mir-203b, hsa-mir-5680, hsa-mir-5681a, mmu-mir-145b, mmu-mir-21b, mmu-mir-21c, hsa-mir-486-2, mmu-mir-126b, mmu-mir-142b, mmu-mir-9b-2, mmu-mir-9b-1, mmu-mir-9b-3
In a number of single studies, miRNAs such as let-7d [26], let-7i [26] and miR-210 [23] were also found to be up-regulated in prostate cancer, in contrast to let-7g [23], miR-27b [28], miR-99a [23], miR-126 [54], miR-128 [26], miR-152 [28], miR-200a [58] and miR-449a [59] which were down-regulated in prostate cancer samples. [score:7]
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33
[+] score: 7
miR-128 was expressed in all samples, notably in CE-RSC neurospheres and the inner plexiform layer of the retina at P4. [score:3]
J: Strong hybridisation signal was detected for miR-128 in the CE-RSC neurospheres (arrowheads). [score:1]
K: In the P4 retina a hybridisation signal for miR-128 was observed in the inner portion of the NBL (arrows) and in some cells of the GCL (arrowheads). [score:1]
L: In the adult retina strongest miR-128 hybridisation signal was detected in the INL (arrowheads), the outer portion of the outer plexiform layer and photoreceptor inner segments (arrows). [score:1]
A range of other candidates with p-values < 0.05 in at least one experimental condition (miR-128, miR-150, miR-204, miR-25, miR-27, miR-326 miR-34, miR-370, miR-378 and miR-485-5p) were selected to represent different predicted patterns of activity or for their lack of previous association with neural tissue. [score:1]
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34
[+] score: 6
Bioinformatics analyzed showed the FAS was targeted of miR-2320 and miR-181a and SERPINE was target of miR-769-3p and miR-128 in p53 signaling pathways 19. [score:5]
To testify if miRNAs in milk-derived exosomes could enter into IPEC-J2 cells, we determined the level of miR-7134, miR-1343, miR-2320, miR-181a, miR-769-3p and miR-128 in IPEC-J2 cells after incubation with exosomes. [score:1]
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35
[+] score: 6
These suggestions are also in line with a previous study by Tan et al. where only 15% of RISC -associated miR-128 target genes, identified by HITS-CLIP, were upregulated after miR-128 deletion 11. [score:6]
[1 to 20 of 1 sentences]
36
[+] score: 6
Profiling of miRNAs expression was also performed in the YAC128 and R6/2 mice, showing that nine miRNAs (miR-22, miR-29c, miR-128, miR-132, miR-138, miR-218, miR-222, miR-344, and miR-674*) are commonly down-regulated in 12-month-old YAC128 mice and 10-week-old R6/2 mice (100). [score:6]
[1 to 20 of 1 sentences]
37
[+] score: 5
Targeting of the Bmi-1 oncogene/stem cell renewal factor by microRNA-128 inhibits glioma proliferation and self-renewal. [score:5]
[1 to 20 of 1 sentences]
38
[+] score: 5
We found that other words among the six most depleted corresponded to the seed regions of 12 more steady-steate highly expressed miRNAs: The mmu-miR-125 family, mmu-miR-137, mmu-miR-128 and the mmu-let-7 family. [score:3]
Many of the miRNAs that were previously linked to neuronal biology (e. g. mmu-miR-124, mmu-miR-125 family, mmu-miR-137, mmu-miR-128, mmu-miR-9 and mmu-let-7) [6, 25- 32, 57, 58] belong to this category. [score:1]
The sixth most depleted word contains a 6-mer complementary to positions 3 - 8 of mmu-miR-137, and the seventh to positions 2 - 8 of miR-128. [score:1]
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39
[+] score: 5
Other miRNAs from this paper: mmu-mir-128-1, dre-mir-128-1, dre-mir-128-2, dre-mir-128-3
Targeting of the Bmi-1 oncogene/stem cell renewal factor by microRNA-128 inhibits glioma proliferation and self-renewal. [score:5]
[1 to 20 of 1 sentences]
40
[+] score: 5
Other miRNAs from this paper: mmu-mir-128-1
Targeting of the Bmi-1 in stem cells by microRNA-128 inhibits glioma proliferation and self-renewal, implying that miRNA-128 may be a therapeutic target agent for the "stem cell-like" characteristics of glioma [81]. [score:5]
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41
[+] score: 5
Among the 6 apoptosis-related miRNAs we selected for, whereas miR-21 was antiapoptotic [33, 34], miR-29b [35, 36], miR-15a and miR-16 [37, 38], miR-128 [39, 40] and miR-98 [41, 42; the present results] were pro-apoptotic. [score:1]
Among them, whereas miR-21, miR-98 and miR-128 showed a fold change greater than 2 (FC>2), miR-15a, miR-16 and miR-29b had a fold change less than 2 (FC<2). [score:1]
For example, our RT-qPCR showed that levels of all the analyzed miRNAs except for miR-128 decreased during this period. [score:1]
In addition, the alteration amplitude of miR-128 detected by microarray was markedly higher than that detected by RT-qPCR. [score:1]
The concentration of Taqman probe was 200 nM for U6, mmu-miR-15a, mmu-miR-16, mmu-miR-21, mmu-miR-29b and mmu-miR-128, and 400 nM for mmu-miR-98. [score:1]
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42
[+] score: 5
For example, miR-625, miR-103/miR-107, miR-21 and miR-301 have been found to promote CRC to invade and metastasize by stimulating multiple metastasis-promoting genes [27– 30], whereas miR-99, miR-137, miR-132 and miR-128 function as tumor suppressors to inhibit the metastasis of CRC [31– 34]. [score:5]
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43
[+] score: 4
The extent of downregulation of miR-128-3p was much less than that of miR-26a at 24 h post-infection. [score:4]
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44
[+] score: 4
However when LY294002 was added, the over expression effects of HIF-1α, VEGF and p-AKT induced by miR-218 were significantly inhibited compared with miR-128 mimic group, P<0.001. [score:4]
[1 to 20 of 1 sentences]
45
[+] score: 4
Other miRNAs from this paper: mmu-mir-128-1
Notably, microRNA-128 has been shown to target components of the NMD system, including Upf1 52, and miR-128 levels are decreased in experimental and human epilepsy 53. [score:3]
However, loss of microRNA-128, which negatively controls levels of Upf1 and another NMD protein 52, results in seizures and premature death in mice 66, suggesting that over-active NMD may contribute to the generation of seizures. [score:1]
[1 to 20 of 2 sentences]
46
[+] score: 4
MiR-15a, miR-17, mir-20a, miR-20b, miR-106a, miR-128, miR-181a, miR-181b, and miR-181d were consistently down regulated (Figure 2C). [score:2]
MiR-128, identified in the brain and thymus, was only down regulated in the latter following a stress response. [score:1]
The individual miRs (miR-150, miR-205, miR-128, miR-181a, miR-181b, miR-181d) were detected by Northern blotting. [score:1]
[1 to 20 of 3 sentences]
47
[+] score: 4
Li et al. demonstrated that insulin -induced ROS production down-regulates miR-145 and miR-128 36. [score:4]
[1 to 20 of 1 sentences]
48
[+] score: 4
The most abundant miRNA, and the third most abundant class of sequences was miR128, a miRNA important for neuronal development, synaptogenesis, and post-mitotic neuronal functioning 45. [score:2]
The third, fourth, seventh, eighth and ninth mapped to neuronal associated microRNAs, including miR128, miR99, miR100, miR22, and miR127 (21–22 nt). [score:1]
The most abundant sequences of sRNAs isolated and sequenced were over 30 nt; however, we did isolate and sequence miRNAs in the 20–21 nt range, including miR128, miR99a, miR100, miR22, and miR127. [score:1]
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49
[+] score: 4
miR-128 regulates neuronal migration, outgrowth and intrinsic excitability via the intellectual disability gene Phf6. [score:2]
Finally, miR-128 was shown to affect migration by regulating PHF6 (Franzoni et al., 2015). [score:2]
[1 to 20 of 2 sentences]
50
[+] score: 3
Here, by sequence matching using bioinformatics analyses, we found quite a few of candidate miRNAs that target Bcl-2, including miR-429, miR-30, miR-22, miR-25, miR-32, miR-92, miR-363, miR-367, miR-99, miR-27, miR-128, etc. [score:3]
[1 to 20 of 1 sentences]
51
[+] score: 3
Other miRNAs from this paper: cel-let-7, cel-lin-4, hsa-let-7a-1, hsa-let-7a-2, hsa-let-7a-3, hsa-let-7b, hsa-let-7c, hsa-let-7d, hsa-let-7e, hsa-let-7f-1, hsa-let-7f-2, hsa-mir-17, hsa-mir-29a, hsa-mir-92a-1, hsa-mir-92a-2, hsa-mir-101-1, hsa-mir-29b-1, hsa-mir-29b-2, mmu-let-7g, mmu-let-7i, mmu-mir-29b-1, mmu-mir-101a, mmu-mir-128-1, mmu-mir-9-2, mmu-mir-132, mmu-mir-138-2, mmu-mir-181a-2, mmu-mir-199a-1, hsa-mir-199a-1, hsa-mir-7-1, hsa-mir-7-2, hsa-mir-7-3, hsa-mir-181a-2, hsa-mir-181b-1, hsa-mir-181c, hsa-mir-199a-2, hsa-mir-181a-1, mmu-let-7d, hsa-let-7g, hsa-let-7i, hsa-mir-128-1, hsa-mir-132, hsa-mir-138-2, hsa-mir-9-1, hsa-mir-9-2, hsa-mir-9-3, hsa-mir-138-1, mmu-let-7a-1, mmu-let-7a-2, mmu-let-7b, mmu-let-7c-1, mmu-let-7c-2, mmu-let-7e, mmu-let-7f-1, mmu-let-7f-2, mmu-mir-29a, mmu-mir-29c, mmu-mir-92a-2, rno-let-7d, rno-mir-7a-1, rno-mir-101b, mmu-mir-101b, hsa-mir-181b-2, mmu-mir-17, mmu-mir-181a-1, mmu-mir-29b-2, mmu-mir-199a-2, mmu-mir-92a-1, mmu-mir-9-1, mmu-mir-9-3, mmu-mir-138-1, mmu-mir-181b-1, mmu-mir-181c, hsa-mir-128-2, mmu-mir-7a-1, mmu-mir-7a-2, mmu-mir-7b, hsa-mir-29c, hsa-mir-101-2, cel-lsy-6, mmu-mir-181b-2, rno-let-7a-1, rno-let-7a-2, rno-let-7b, rno-let-7c-1, rno-let-7c-2, rno-let-7e, rno-let-7f-1, rno-let-7f-2, rno-let-7i, rno-mir-7a-2, rno-mir-7b, rno-mir-9a-1, rno-mir-9a-3, rno-mir-9a-2, rno-mir-17-1, rno-mir-29b-2, rno-mir-29a, rno-mir-29b-1, rno-mir-29c-1, rno-mir-92a-1, rno-mir-92a-2, rno-mir-101a, rno-mir-128-1, rno-mir-128-2, rno-mir-132, rno-mir-138-2, rno-mir-138-1, rno-mir-181c, rno-mir-181a-2, rno-mir-181b-1, rno-mir-181b-2, rno-mir-199a, rno-mir-181a-1, rno-mir-421, hsa-mir-181d, hsa-mir-92b, hsa-mir-421, mmu-mir-181d, mmu-mir-421, mmu-mir-92b, rno-mir-17-2, rno-mir-181d, rno-mir-92b, rno-mir-9b-3, rno-mir-9b-1, rno-mir-9b-2, mmu-mir-101c, mmu-let-7j, mmu-let-7k, rno-let-7g, rno-mir-29c-2, rno-mir-29b-3, mmu-mir-9b-2, mmu-mir-9b-1, mmu-mir-9b-3
Mouse miR-124a as well as miR-128, miR-101 and miR-132 have been reported to be expressed specifically in brain [15]. [score:3]
[1 to 20 of 1 sentences]
52
[+] score: 3
Expression vectors of miR-128, miR-152, and miR-363 were constructed using the same method. [score:3]
[1 to 20 of 1 sentences]
53
[+] score: 3
Nrf2 (+/+) Saline—Nrf2(–/–) Saline miR-128, miR-7a, miR-669c, miR-298, miR-543, miR-770-5p, miR-669b* and miR-544-5p S1 Changes in miRNA expression profile after exposure to paraquat. [score:3]
[1 to 20 of 1 sentences]
54
[+] score: 3
Other miRNAs, miR-128 (Bcap29), miR-3064-3p (Pik3cg), miR-3074-5p (Twistnb) and miR-485 (Dgkb) decreased the luciferase expression of the pGL3 control empty vector to the same degree as the vector containing the cloned 3′UTR (Figure 2C and data not shown). [score:3]
[1 to 20 of 1 sentences]
55
[+] score: 3
Genes associated with ubiquitin -mediated proteolysis, cell cycle, NF-kB and insulin signalling, as well as miRs miR-132, miR-122, miR-499, miR-128 and miR-22 formed central nodes in the network of miRNA:target interactions disrupted during ageing (Fig. S2). [score:3]
[1 to 20 of 1 sentences]
56
[+] score: 3
In addition, miR-128, which expressed specifically in brain, did not detecte in EVs associated with caveolin-3 in wt mice, although miR-128 in other all of EVs were detected (S3B Fig). [score:3]
[1 to 20 of 1 sentences]
57
[+] score: 3
More recently, a neuronal miRNA, miR-128, was shown to modulate the expression of BAG2, a cochaperone potentially involved in tau degradation and aggregation in cultured COS-7 cells and in primary neurons [24]. [score:3]
[1 to 20 of 1 sentences]
58
[+] score: 3
CEBPD reduced the levels of miR-26b, miR-29a, and miR-128 that are predicted to target inducible nitric oxide synthase [10]. [score:3]
[1 to 20 of 1 sentences]
59
[+] score: 3
Previous studies have identified miR-21, miR-27, miR-96, miR-128, miR-155 and miR-182 as oncogenes, and miR-17, miR-27, miR-125, miR-145, miR-205 and miR-206 as tumor suppressor genes [13- 15]. [score:3]
[1 to 20 of 1 sentences]
60
[+] score: 2
In situ hybridization In situ hybridization was performed as previously described previously (38) using 10 μm fresh frozen OE cryosections and LNA probes against miR-741, miR-9 and miR-128 (Exigen). [score:1]
In situ hybridization was performed as previously described previously (38) using 10 μm fresh frozen OE cryosections and LNA probes against miR-741, miR-9 and miR-128 (Exigen). [score:1]
[1 to 20 of 2 sentences]
61
[+] score: 2
For the mir-101 and mir-128 families, two members were identified in each; mir-101a and mir-101b, and mir-128-1 and mir-128-2. 414 miRNAs were common amongst the infected and sham-infected (control) groups (Figure  1). [score:1]
These 16 miRNAs belonged to 7 families; let-7, mir-101, mir-128, mir-107, mir-140, mir-29a and mir-124. [score:1]
[1 to 20 of 2 sentences]
62
[+] score: 2
MicroRNA-128 inhibitor attenuates the apoptosis of cardiomyocytes during M-I/R injury through the activation of peroxisome proliferator-activated receptor gamma [25]. [score:2]
[1 to 20 of 1 sentences]
63
[+] score: 2
MiR-124 may act together with miR-137 and miR-128 synergistically to regulate neural cells 25. [score:2]
[1 to 20 of 1 sentences]
64
[+] score: 2
These findings suggest miR-22 normally restrains development of a contralateral epileptogenic focus in this mo del and loss of miR-22, as with loss of miR-128 28, is pro-epileptic. [score:2]
[1 to 20 of 1 sentences]
65
[+] score: 2
To determine whether the observed delay in accumulation of mature miRNAs was specific to pri-miR-183/96/182, we measured the levels of pri-miRNAs and mature miRNAs for neuronal miR-128 and ubiquitously expressed miR-16 in developing retina. [score:1]
No delays in processing, similar to that seen for miR-183/96/182, were observed for miR-128 or miR-16 (Supplementary Fig. 1f). [score:1]
[1 to 20 of 2 sentences]
66
[+] score: 2
Modulation of Pri-miR processing is especially relevant to the proper regulation of neuro-specific and neuro-enriched miRNAs, including let-7 family members, miR-128 and miR-138, whose post-transcriptional maturation may dramatically increase with the transition from stem cells to post-mitotic differentiated elements [53- 55]. [score:2]
[1 to 20 of 1 sentences]
67
[+] score: 2
In various studies, several miRNAs, such as miR-451, miR-128, and miR-34, apparently regulate cancer stemness and drug resistance in breast cancer [7]. [score:2]
[1 to 20 of 1 sentences]
68
[+] score: 2
Other miRNAs from this paper: hsa-let-7a-1, hsa-let-7a-2, hsa-let-7a-3, hsa-let-7b, hsa-let-7c, hsa-let-7d, hsa-let-7e, hsa-let-7f-1, hsa-let-7f-2, hsa-mir-26a-1, hsa-mir-26b, hsa-mir-27a, hsa-mir-29a, hsa-mir-32, hsa-mir-33a, hsa-mir-99a, hsa-mir-103a-2, hsa-mir-103a-1, hsa-mir-107, mmu-let-7g, mmu-let-7i, mmu-mir-15b, mmu-mir-99a, mmu-mir-126a, mmu-mir-128-1, mmu-mir-130a, mmu-mir-140, mmu-mir-154, mmu-mir-204, mmu-mir-143, hsa-mir-204, hsa-mir-211, hsa-mir-218-1, hsa-mir-218-2, hsa-mir-222, hsa-mir-223, mmu-mir-301a, mmu-mir-34c, mmu-mir-34b, mmu-let-7d, hsa-let-7g, hsa-let-7i, hsa-mir-15b, hsa-mir-128-1, hsa-mir-130a, hsa-mir-140, hsa-mir-143, hsa-mir-126, hsa-mir-129-2, hsa-mir-154, mmu-let-7a-1, mmu-let-7a-2, mmu-let-7b, mmu-let-7c-1, mmu-let-7c-2, mmu-let-7e, mmu-let-7f-1, mmu-let-7f-2, mmu-mir-26a-1, mmu-mir-26b, mmu-mir-29a, mmu-mir-29c, mmu-mir-27a, mmu-mir-129-2, mmu-mir-103-1, mmu-mir-103-2, mmu-mir-340, mmu-mir-107, mmu-mir-32, mmu-mir-218-1, mmu-mir-218-2, mmu-mir-223, mmu-mir-26a-2, mmu-mir-211, mmu-mir-222, hsa-mir-128-2, hsa-mir-29c, hsa-mir-101-2, hsa-mir-34b, hsa-mir-34c, hsa-mir-301a, hsa-mir-26a-2, hsa-mir-379, mmu-mir-379, hsa-mir-340, mmu-mir-409, hsa-mir-409, hsa-mir-499a, hsa-mir-455, hsa-mir-670, mmu-mir-1249, mmu-mir-670, mmu-mir-499, mmu-mir-455, bta-mir-26a-2, bta-mir-29a, bta-let-7f-2, bta-mir-101-2, bta-mir-103-1, bta-mir-16b, bta-mir-222, bta-mir-26b, bta-mir-27a, bta-mir-499, bta-mir-99a, bta-mir-126, bta-mir-128-1, bta-mir-34b, bta-mir-107, bta-mir-140, bta-mir-15b, bta-mir-218-2, bta-let-7d, bta-mir-29c, bta-mir-455, bta-let-7g, bta-let-7a-1, bta-let-7f-1, bta-let-7i, bta-mir-34c, bta-let-7a-2, bta-let-7a-3, bta-let-7b, bta-let-7c, bta-let-7e, bta-mir-103-2, bta-mir-204, hsa-mir-1249, hsa-mir-1306, hsa-mir-103b-1, hsa-mir-103b-2, bta-mir-128-2, bta-mir-129-2, bta-mir-130a, bta-mir-143, bta-mir-154a, bta-mir-211, bta-mir-218-1, bta-mir-223, bta-mir-26a-1, bta-mir-301a, bta-mir-32, bta-mir-33a, bta-mir-340, bta-mir-379, bta-mir-409a, bta-mir-670, mmu-mir-1306, bta-mir-1306, bta-mir-1249, bta-mir-2284i, bta-mir-2285a, bta-mir-2284s, bta-mir-2285d, bta-mir-2284l, bta-mir-2284j, bta-mir-2284t, bta-mir-2285b-1, bta-mir-2284d, bta-mir-2284n, bta-mir-2284g, bta-mir-2284p, bta-mir-2284u, bta-mir-2284f, bta-mir-2284a, bta-mir-2284k, bta-mir-2284c, bta-mir-2284v, bta-mir-2285c, bta-mir-2284q, bta-mir-2284m, bta-mir-2284b, bta-mir-2284r, bta-mir-2284h, bta-mir-2284o, bta-mir-2284e, hsa-mir-1260b, bta-mir-2284w, bta-mir-2284x, bta-mir-409b, hsa-mir-499b, bta-mir-1260b, bta-mir-2284y-1, bta-mir-2285e-1, bta-mir-2285e-2, bta-mir-2285f-1, bta-mir-2285f-2, bta-mir-2285g-1, bta-mir-2285h, bta-mir-2285i, bta-mir-2285j-1, bta-mir-2285j-2, bta-mir-2285k-1, bta-mir-2285l, bta-mir-6119, mmu-let-7j, bta-mir-2285o-1, bta-mir-2285o-2, bta-mir-2285n-1, bta-mir-2285n-2, bta-mir-2285p, bta-mir-2285m-1, bta-mir-2285m-2, bta-mir-2284y-2, bta-mir-2285n-3, bta-mir-2285n-4, bta-mir-2284y-3, bta-mir-154c, bta-mir-154b, bta-mir-2285o-3, bta-mir-2285o-4, bta-mir-2285m-3, bta-mir-2284y-4, bta-mir-2284y-5, bta-mir-2284y-6, bta-mir-2285m-4, bta-mir-2285o-5, bta-mir-2285m-5, bta-mir-2285n-5, bta-mir-2285n-6, bta-mir-2284y-7, bta-mir-2285n-7, bta-mir-2284z-1, bta-mir-2284aa-1, bta-mir-2285k-2, bta-mir-2284z-3, bta-mir-2284aa-2, bta-mir-2284aa-3, bta-mir-2285k-3, bta-mir-2285k-4, bta-mir-2284z-4, bta-mir-2285k-5, bta-mir-2284z-5, bta-mir-2284z-6, bta-mir-2284z-7, bta-mir-2284aa-4, bta-mir-2285q, bta-mir-2285r, bta-mir-2285s, bta-mir-2285t, bta-mir-2285b-2, bta-mir-2285v, bta-mir-2284z-2, mmu-let-7k, mmu-mir-126b, bta-mir-2285g-2, bta-mir-2285g-3, bta-mir-2285af-1, bta-mir-2285af-2, bta-mir-2285y, bta-mir-2285w, bta-mir-2285x, bta-mir-2285z, bta-mir-2285u, bta-mir-2285aa, bta-mir-2285ab, bta-mir-2284ab, bta-mir-2285ac, bta-mir-2285ad, bta-mir-2284ac, bta-mir-2285ae, chi-let-7a, chi-let-7b, chi-let-7c, chi-let-7d, chi-let-7e, chi-let-7f, chi-let-7g, chi-let-7i, chi-mir-103, chi-mir-107, chi-mir-1249, chi-mir-126, chi-mir-1306, chi-mir-130a, chi-mir-140, chi-mir-143, chi-mir-154a, chi-mir-154b, chi-mir-15b, chi-mir-16b, chi-mir-204, chi-mir-211, chi-mir-222, chi-mir-223, chi-mir-2284a, chi-mir-2284b, chi-mir-2284c, chi-mir-2284d, chi-mir-2284e, chi-mir-26a, chi-mir-26b, chi-mir-27a, chi-mir-29a, chi-mir-29c, chi-mir-301a, chi-mir-33a, chi-mir-340, chi-mir-34b, chi-mir-34c, chi-mir-379, chi-mir-409, chi-mir-455, chi-mir-499, chi-mir-99a, bta-mir-2285ag, bta-mir-2285ah, bta-mir-2285ai, bta-mir-2285aj, bta-mir-2285ak, bta-mir-2285al, bta-mir-2285am, bta-mir-2285ar, bta-mir-2285as-1, bta-mir-2285as-2, bta-mir-2285as-3, bta-mir-2285at-1, bta-mir-2285at-2, bta-mir-2285at-3, bta-mir-2285at-4, bta-mir-2285au, bta-mir-2285av, bta-mir-2285aw, bta-mir-2285ax-1, bta-mir-2285ax-2, bta-mir-2285ax-3, bta-mir-2285ay, bta-mir-2285az, bta-mir-2285an, bta-mir-2285ao-1, bta-mir-2285ao-2, bta-mir-2285ap, bta-mir-2285ao-3, bta-mir-2285aq-1, bta-mir-2285aq-2, bta-mir-2285ba-1, bta-mir-2285ba-2, bta-mir-2285bb, bta-mir-2285bc, bta-mir-2285bd, bta-mir-2285be, bta-mir-2285bf-1, bta-mir-2285bf-2, bta-mir-2285bf-3, bta-mir-2285bg, bta-mir-2285bh, bta-mir-2285bi-1, bta-mir-2285bi-2, bta-mir-2285bj-1, bta-mir-2285bj-2, bta-mir-2285bk, bta-mir-2285bl, bta-mir-2285bm, bta-mir-2285bn, bta-mir-2285bo, bta-mir-2285bp, bta-mir-2285bq, bta-mir-2285br, bta-mir-2285bs, bta-mir-2285bt, bta-mir-2285bu-1, bta-mir-2285bu-2, bta-mir-2285bv, bta-mir-2285bw, bta-mir-2285bx, bta-mir-2285by, bta-mir-2285bz, bta-mir-2285ca, bta-mir-2285cb, bta-mir-2285cc, bta-mir-2285cd, bta-mir-2285ce, bta-mir-2285cf, bta-mir-2285cg, bta-mir-2285ch, bta-mir-2285ci, bta-mir-2285cj, bta-mir-2285ck, bta-mir-2285cl, bta-mir-2285cm, bta-mir-2285cn, bta-mir-2285co, bta-mir-2285cp, bta-mir-2285cq, bta-mir-2285cr-1, bta-mir-2285cr-2, bta-mir-2285cs, bta-mir-2285ct, bta-mir-2285cu, bta-mir-2285cv-1, bta-mir-2285cv-2, bta-mir-2285cw-1, bta-mir-2285cw-2, bta-mir-2285cx, bta-mir-2285cy, bta-mir-2285cz, bta-mir-2285da, bta-mir-2285db, bta-mir-2285dc, bta-mir-2285dd, bta-mir-2285de, bta-mir-2285df, bta-mir-2285dg, bta-mir-2285dh, bta-mir-2285di, bta-mir-2285dj, bta-mir-2285dk, bta-mir-2285dl-1, bta-mir-2285dl-2, bta-mir-2285dm
In addition, among these ten miRNA, mir-128-2, mir-218-2 and mir-301a were found in the ARPP21 (cAMP-regulated phosphoprotein), SLIT3 (Slit homolog 3) and SKA2 (Spindle and kinetochore associated complex subunit 2) genes in human, mouse, cow and chicken [65]. [score:2]
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miR-124 is one of the five most abundant miRNAs (miR-99a-5p, miR-128, miR-124, miR-22-3p, and miR-99b-5p) embedded in the human circulating vesicles [36], which suggests a high priority in the regulation of ECs’ behaviors. [score:2]
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Three brain-enriched miRNAs, miR-9, Let-7, and miR-128, were utilized. [score:1]
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Other miRNAs from this paper: mmu-mir-128-1, hsa-mir-128-1, hsa-mir-128-2
Recently, a specific microRNA, mir-128, was found to bind L1 RNA and repress its integration in HeLa and induced pluripotent stem cells (iPSCs) [192]. [score:1]
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Morphine modulates cell proliferation through mir133b &mir128 in the neuroblastoma SH-SY5Y cell line. [score:1]
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However, in sheep, the analyzed miRNA sites that are located in the 505 bp 3′ UTR of the ovine s-SCF (+) form belongs to the miRNA families of miR-27a/b, miR-194, miR-128, miR-370, and two sites for miR-132/212, miR-320/320abcd (Figure 9(a)) where as miR-669f/a/o-3p, miR-466b and miR828b are detected on the shorter 3′ UTR segment (144 bp) of ovine m-SCF (−) form (Figure 9(b)). [score:1]
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Eleven miRNAs were randomly selected for qPCR analysis for each age: GD 17.0 miR-1843-5p, miR-485-3p, miR-711, miR-3962, miR-3067-3p, miR-212-3p, miR-669i, miR-877, miR-26b-3p, miR-465c-3p, let-7b-3p; GD 18.0 miR-1843-5p, miR-485-3p, miR-3473d, miR-132-5p, miR-3074-1-3p, miR-128-2-5p, miR-130b-5p, miR-490-5p, miR-669h-3p, miR-3058-5p, miR-146b. [score:1]
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Other miRNAs from this paper: hsa-let-7a-1, hsa-let-7a-2, hsa-let-7a-3, hsa-let-7f-1, hsa-let-7f-2, hsa-mir-16-1, hsa-mir-17, hsa-mir-19a, hsa-mir-19b-1, hsa-mir-19b-2, hsa-mir-23a, hsa-mir-26a-1, hsa-mir-26b, hsa-mir-27a, hsa-mir-29a, hsa-mir-30a, hsa-mir-31, hsa-mir-100, hsa-mir-29b-1, hsa-mir-29b-2, hsa-mir-16-2, mmu-mir-23b, mmu-mir-27b, mmu-mir-29b-1, mmu-mir-30a, mmu-mir-30b, mmu-mir-127, mmu-mir-128-1, mmu-mir-132, mmu-mir-133a-1, mmu-mir-188, mmu-mir-194-1, mmu-mir-195a, mmu-mir-199a-1, hsa-mir-199a-1, mmu-mir-200b, mmu-mir-205, mmu-mir-206, hsa-mir-30c-2, hsa-mir-30d, mmu-mir-122, mmu-mir-30e, hsa-mir-199a-2, hsa-mir-199b, hsa-mir-205, hsa-mir-211, hsa-mir-212, hsa-mir-214, hsa-mir-217, hsa-mir-200b, hsa-mir-23b, hsa-mir-27b, hsa-mir-30b, hsa-mir-122, hsa-mir-128-1, hsa-mir-132, hsa-mir-133a-1, hsa-mir-133a-2, hsa-mir-127, hsa-mir-138-1, hsa-mir-188, hsa-mir-194-1, hsa-mir-195, hsa-mir-206, mmu-mir-19b-2, mmu-mir-30c-1, mmu-mir-30c-2, mmu-mir-30d, mmu-mir-200a, mmu-let-7a-1, mmu-let-7a-2, mmu-let-7f-1, mmu-let-7f-2, mmu-mir-16-1, mmu-mir-16-2, mmu-mir-23a, mmu-mir-26a-1, mmu-mir-26b, mmu-mir-29a, mmu-mir-29c, mmu-mir-27a, mmu-mir-31, mmu-mir-351, hsa-mir-200c, mmu-mir-17, mmu-mir-19a, mmu-mir-100, mmu-mir-200c, mmu-mir-212, mmu-mir-214, mmu-mir-26a-2, mmu-mir-211, mmu-mir-29b-2, mmu-mir-199a-2, mmu-mir-199b, mmu-mir-19b-1, mmu-mir-138-1, hsa-mir-128-2, mmu-mir-217, hsa-mir-194-2, mmu-mir-194-2, hsa-mir-29c, hsa-mir-30c-1, hsa-mir-200a, hsa-mir-30e, hsa-mir-26a-2, hsa-mir-379, mmu-mir-379, mmu-mir-133a-2, mmu-mir-133b, hsa-mir-133b, mmu-mir-412, mmu-mir-431, hsa-mir-431, hsa-mir-451a, mmu-mir-451a, mmu-mir-467a-1, hsa-mir-412, hsa-mir-485, hsa-mir-487a, hsa-mir-491, hsa-mir-503, hsa-mir-504, mmu-mir-485, hsa-mir-487b, mmu-mir-487b, mmu-mir-503, hsa-mir-556, hsa-mir-584, mmu-mir-665, mmu-mir-669a-1, mmu-mir-674, mmu-mir-690, mmu-mir-669a-2, mmu-mir-669a-3, mmu-mir-669c, mmu-mir-696, mmu-mir-491, mmu-mir-504, hsa-mir-665, mmu-mir-467e, mmu-mir-669k, mmu-mir-669f, hsa-mir-664a, mmu-mir-1896, mmu-mir-1894, mmu-mir-1943, mmu-mir-1983, mmu-mir-1839, mmu-mir-3064, mmu-mir-3072, mmu-mir-467a-2, mmu-mir-669a-4, mmu-mir-669a-5, mmu-mir-467a-3, mmu-mir-669a-6, mmu-mir-467a-4, mmu-mir-669a-7, mmu-mir-467a-5, mmu-mir-467a-6, mmu-mir-669a-8, mmu-mir-669a-9, mmu-mir-467a-7, mmu-mir-467a-8, mmu-mir-669a-10, mmu-mir-467a-9, mmu-mir-669a-11, mmu-mir-467a-10, mmu-mir-669a-12, mmu-mir-3473a, hsa-mir-23c, hsa-mir-4436a, hsa-mir-4454, mmu-mir-3473b, hsa-mir-4681, hsa-mir-3064, hsa-mir-4436b-1, hsa-mir-4790, hsa-mir-4804, hsa-mir-548ap, mmu-mir-3473c, mmu-mir-5110, mmu-mir-3473d, mmu-mir-5128, hsa-mir-4436b-2, mmu-mir-195b, mmu-mir-133c, mmu-mir-30f, mmu-mir-3473e, hsa-mir-6825, hsa-mir-6888, mmu-mir-6967-1, mmu-mir-3473f, mmu-mir-3473g, mmu-mir-6967-2, mmu-mir-3473h
Hcy also induces alteration of miRNAs related to tight junctions signaling such as miR-128, miR-132, miR-133, miR-195, miR-3473, miR-19, miR-200, miR-205, miR-214, miR-217, miR-23, miR-26, miR-29, miR-30, miR-31 AND miR-690. [score:1]
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Three miRNAs in FCx (miR-128, miR-129-5p, and miR-344) and one miRNA in HP (miR-7a) map to two chromosomal loci (Table S1). [score:1]
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