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64 publications mentioning mmu-mir-127

Open access articles that are associated with the species Mus musculus and mention the gene name mir-127. 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: 380
Other miRNAs from this paper: hsa-mir-127, mmu-mir-433, hsa-mir-433
0065256.g005 Figure 5(A-C) qPCR analysis of c-Jun (A), miR-127 (B), and MMP13 (C) mRNA expression in MHCC97H cells treated with TGFβR inhibitor (SB 431542, 10 µM), NFκB inhibitor (BAY-11-7082, 5 µM, ERK inhibitor (PD 98059, 50 µM), p38 inhibitor (SB 203580, 10 µM) and JNK inhibitor (SP 600125, 50 µM),) in the absence (−) or presence of TGFβ (+) (5 ng/ml). [score:13]
The miR-127 was downregulated in four out of five HCC (Fig. 6A), and the downregulation of miR-127 correlated negatively with the upregulation of MMP13 mRNA and protein (Fig. 6B). [score:10]
In addition, MMP13 mRNA showed similar changes as its protein upon inhibition or overexpression of miR-127 (not shown), which was in agreement with the inference that a miRNA also represses its target gene mRNA [16]. [score:7]
Overexpression of miR-127 inhibits MMP13 3′UTR activity and gene expression. [score:7]
MHCC97H cells were transfected with either an empty vector pTarget (-) or a miR-127 expression vector in pTarget (+) (2 µg). [score:7]
MHCC97H cells were transfected with pTarget or pTarget-miR127 (2 µg), a negative (neg) control or miR-127 inhibitor (anti-miR-127) (20 nM). [score:7]
Overall, the results demonstrate that TGFβ represses miR-127 expression and activates MMP13 expression through c-Jun mediated ERK and JNK pathways, and NFkB signaling is not involved in such regulation. [score:6]
Overall, our studies establish a novel feedback regulatory network between miR-127 and the TGFβ signaling, whereby miR-127 constrains TGFβ activation of HCC cell migration via inhibition of MMP13 function, and TGFβ represses miR-127 expression via activation of c-Jun. [score:6]
Mo del of negative-feedback regulation of miR-127 expression by TGFβ/c-Jun that controls MMP13 expression and stability in HCC. [score:6]
It is noteworthy that miR-127 expression is downregulated in a subset of HCC specimens we analyzed. [score:6]
Two algorithms, TargetScan and miRanda, were used to predict miR-127 target genes that are involved in regulating cell migration/invasion. [score:6]
On the other hand, PPP1R9B (protein phosphatase 1, regulatory subunit 9B) was also a predicted target of miR-127, but its 3′UTR reporter activity was not altered by miR-127 expression (Fig. 2B, middle). [score:6]
Indeed, transient transfection assays showed that overexpression of c-Jun, but not c-Fos, dose -dependently inhibited miR-127 promoter activity (Fig. 4B), and the inhibition of c-Jun was further enhanced by TGFβ (Fig. 4C, left). [score:6]
MHCC97H cells were transfected with pTarget or pTarget-miR127 (2 µg), and seeded onto pre-coated inserts with BME solution and incubated for 16 hr. [score:5]
In addition, overexpression of p53 (Fig. 4F, left) induced miR-127 expression in MHCC97H cells and the effect of p53 was blocked by c-Jun (Fig. 4F, right). [score:5]
A recent report showed that upregulation of miR-127-3p was associated with KRAS mutation in colorectal cancer [11]. [score:5]
The miR-127 expression plasmid pTarget-miR-127 was generated as described [3]. [score:5]
The activation of c-Jun serves a dual function, which involves induction of MMP13 gene expression but repression of miR-127 gene transcription by inhibiting miR-127 promoter activity. [score:5]
Overexpression of miR-127 inhibits HCC cell migration and tumor growth. [score:5]
Next, we established control and miR-127 overexpressing cells that also express a constitutive luciferase reporter (see M&M section), which are designated as 97HLuc-Sico (control) and 97HLuc-miR-127 (Fig. 1D, left). [score:5]
MHCC97H and Hepa-1 cells were transfected with pTarget or pTarget-miR-127 (2 µg), in the absence or presence of TGFβ (5 ng/ml). [score:5]
TGFβ Enhances AP1 -mediated Suppression of miR-127 Expression. [score:5]
Second, we elucidated the underlying molecular basis by identifying MMP13, a gene downstream of the TGFβ signaling that is important in tumor invasion and metastasis, as a target for miR-127 inhibition. [score:5]
Consistent with these results, inhibition of endogenous miR-127 expression by a specific anti-miR-127 increased MMP13 3′UTR activity (Fig. 2C). [score:5]
Consistently, the repression of miR-127 by TGFβ was relieved by TGFβR, ERK, and JNK inhibitors, but not by an NFkB inhibitor (Fig. 5B). [score:5]
Briefly, MHCC97H cells (1×10 [6], 6-cm plate) were cultured overnight and transfected with pTarget or pTarget-miR-127 the next day using Lipofactamine 2000 (Invitrogen). [score:5]
Overexpression of miR-127 inhibits MMP13 and TGFβ -mediated induction of HCC cell migration. [score:5]
MHCC97H cells were transfected with MMP13 siRNA (siMMP13) (20 nM) in the absence or presence of pTarget or pTarget-miR-127 (2 µg). [score:5]
Hela cells were co -transfected with the control pTarget (0), pTarget-miR-127, and MMP13 (left), PPP1R9B (middle), or MMP13 mutant (mut) 3′UTRs (right). [score:5]
However, miRNA expression profiling in early stage invasive squamous cell carcinomas (ISCC) revealed a significant correlation between the increased expression of miR-127 and lymph mode metastasis [6]. [score:5]
In contrast, knockdown of endogenous miR-127 using a specific miR-127 inhibitor (anti-miR-127) facilitated MHCC97H cell migration (Fig. 1B, right two). [score:4]
miR-127 is downregulated in a subset of HCC specimens. [score:4]
The results further support MMP13 as a target of miR-127, and also establish the functionality of miR-127 and MMP13 in the development of HCC. [score:4]
The effect of miR-127 is through direct inhibition of TGFβ -mediated activation of matrix metallopeptidase 13 (MMP13, also known as collagenase-3). [score:4]
We further show that the activation of TGFβ signature in a subset of HCC is at least in part attributed to the downregulation of miR-127. [score:4]
miR-127 is Downregulated in a Subset of HCC Specimens. [score:4]
Therefore, HepG2 cells were used to examine the effect of transient p53 knockdown on miR-127 expression. [score:4]
Interestingly, TGFβ inhibits miR-127 transcription through activation of c-Jun via extracellular signal-regulated kinases (ERK) and the c-Jun amino-terminal kinases (JNK) pathways, which counteracts the stimulation of miR-127 by p53. [score:4]
In addition, miR-127 was part of the miRNA signature that was upregulated in acute myeloid leukaemia (AML) [7] and in nodal diffuse large B-cell lymphomas [8]. [score:4]
Fifth, we demonstrated that miR-127 is downregulated in a subset of HCC specimens that have active MMP13. [score:4]
Importantly, the TGFβ signature only occurred in a subset of HCC displaying invasive phenotype [29], [30] and the downregulation of miR-127 correlated with the activation of MMP13/TGFβ signaling. [score:4]
Overexpression of p53 induced miR-127 promoter transactivation, which was antagonized by c-Jun (Fig. 4D), suggesting a direct activation of miR-127 transcription by p53. [score:4]
Although downregulation of miR-127 was observed in rat liver during hepatocarcinogenesis [10], the functional role of miR-127 in HCC has remained elusive until now. [score:4]
Overall, the results demonstrate that MMP13 is a direct target gene of miR-127. [score:4]
Treatment of MHCC97H cells with a recombinant human MMP13 protein markedly increased HCC cell migration, which was significantly attenuated by miR-127 overexpression (Fig. 3A). [score:3]
miR-127 Inhibits HCC Cell Migration and Invasion. [score:3]
The major focus is to determine the inhibitory effect of miR-127 in HCC cell migration and/or invasion, thus a higher invasive cell line, i. e. MHCC97H, was chosen to be the most appropriate cell mo del for our study. [score:3]
Interestingly, miR-127 repression by TGFβ was also blunted by the p38 MAPKs inhibitor, suggesting an alternate mechanism not involving c-Jun. [score:3]
As expected, TGFβ treatment induced MHCC97H migration and its effect was markedly blunted by co -expression of miR-127 (Fig. 3D). [score:3]
The microRNA-127 (miR-127) is located within the imprinted Dlk1/Gtl2 region expressed from the maternal chromosome [1]. [score:3]
On the other hand, overexpression of miR-127 did not affect TGFβ activation of c-Jun (not shown). [score:3]
The results provide evidence for miR-127 inhibition of TGFβ -mediated HCC migration. [score:3]
TGFβ represses miR-127 expression by enhancing c-Jun activity. [score:3]
On the other hand, overexpression of miR-127 decreases MMP13 protein levels by binding to its 3′UTR and causing MMP13 degradation, thus diminishing TGFβ -mediated HCC migration. [score:3]
The first report suggesting that miR-127 is a putative tumor suppressor was based on observations that miR-127 levels were induced by the chromatin-modifying drug 5′-aza-2′-deoxycytidine (Aza) in a panel of human cancer cell lines including T24, HCT116, Hela, NCCIT, and Ramos cells [5]. [score:3]
0065256.g004 Figure 4(A) qPCR analysis of MMP13 (left), c-Jun (middle), and miR-127 (right) expression in MHCC97H cells treated with TGFβ. [score:3]
When the miR-127 seed region in the MMP13 3′UTR was mutated, the suppression of MMP13 3′UTR activity by miR-127 was relieved (Fig. 2B, right). [score:3]
0065256.g006 Figure 6(A-B) qPCR analysis of miR-127 expression (A) and MMP13 mRNA (B, left), and Western blot (WB) analysis of MMP13 protein (B, right) in 5 pairs of surrounding controls and HCC specimens. [score:3]
Interestingly, TGFβ induced c-Jun mRNA (Fig. 4A, middle) but inhibited miR-127 levels (Fig. 4A, right) in a dose -dependent fashion. [score:3]
First, we defined a role of miR-127 in inhibiting HCC migration. [score:3]
miR-127 Decreases MMP13 3′UTR Reporter Activity and Protein Expression. [score:3]
Hela cells were co -transfected with miR-127 promoter (pro) luciferase (luc) reporter, and c-Jun or c-Fos expression plasmids. [score:3]
Fourth, we showed that ERK and JNK pathways are involved in TGFβ-induction of c-Jun to activate the expression of MMP13 and repress miR-127. [score:3]
pTarget in MMP13 group; [§]p<0.01, miR-127 vs. [score:3]
Our results demonstrate for the first time that miR-127 serves as a potential tumor suppressor in HCC by antagonizing TGFβ -mediated HCC cell migration. [score:3]
This has limited our ability to test the in vivo effect of miR-127 in the inhibition of HCC metastasis. [score:3]
pTarget in control group; [‡]p<0.01, miR-127 vs. [score:3]
Generation of miR-127 Expressing Cells. [score:3]
pTarget control; [¥]p<0.01, anti-miR-127 vs. [score:3]
Future studies will be focused on using miR-127 knockout mouse mo del to further examine the function of miR-127 in HCC development and the use of this miR as a potential agent to diminish the amplified TGFβ signaling and modulate the invasiveness of HCC cells. [score:3]
We show that overexpression of miR-127 represses HCC migration, invasion, and tumor growth. [score:3]
qPCR confirmed that miR-127 was ∼2-fold increased in 97HLuc-miR-127 cells, which was consistent with the published literature that used the same miR-127 expression system [12]. [score:3]
Nonetheless, our present studies establish for the first time a role of miR-127 in inhibiting HCC invasion in vitro and HCC growth in vivo. [score:3]
Because activation of TGFβ initiates multiple signaling pathways [25], [26], we sought to determine the specific pathways that are involved in the inhibition of miR-127 by c-Jun downstream of the TGFβ signaling. [score:3]
The human, mouse and rat MMP13 3′UTR shared the same seed region for miR-127 (Fig. 2A), thus MMP13 was predicated to be a target of miR-127. [score:3]
The results suggest that miR-127 is likely to function as an inhibitor of HCC. [score:3]
TGFβ Represses miR-127 Expression Through c-Jun Mediated ERK and JNK Pathways. [score:3]
This observation suggests that TGFβ can feedback repress miR-127 expression through both c-Jun -dependent and independent mechanisms. [score:3]
In spite of relatively low efficiency of anti-miR-127, the abundance of MMP13 protein in whole cell lysate was increased by anti-miR-127 and reduced by miR-127 overexpression (Fig. 2D). [score:3]
Third, we identified c-Jun as a transcriptional repressor and p53 an activator of miR-127 expression. [score:3]
Transient transfection assays showed that the MMP13 3′UTR reporter activity was decreased in a dose -dependent fashion by ectopic expression of miR-127 (Fig. 2B, left). [score:2]
Ectopic expression of miR-127 in 97HLuc-miR-127 cells decreased tumor growth compared with the 97HLuc-Sico cells by day 9 (Fig. 1D, right). [score:2]
We analyzed miR-127 expression in five HCC specimens (T) and compared it with matched normal surrounding livers (N) [27]. [score:2]
Overall, the results suggest that miR-127 directly counteracts the effect of MMP13 on HCC cell migration. [score:2]
The invasive potential of MHCC97H cells was similarly diminished by miR-127 expression as determined by a Transwell cell invasion assay (Fig. 1C). [score:2]
It should be noted that other unidentified miR-127 targets may also be involved in miR-127 regulation of HCC cell migration and invasion, which is currently under investigation. [score:2]
Hela cells were co -transfected with miR-127 promoter reporter, c-Jun (100 ng) and/or p53 plasmids (100 ng). [score:1]
In human breast cancer [9] and in a rat mo del of liver carcinogenesis induced by a methyl -deficient diet [10], the levels of miR-127 were decreased. [score:1]
We therefore determined the interaction between miR-127 and TGFβ in controlling HCC cell migration. [score:1]
The results suggest that TGFβ is likely to repress miR-127 through c-Jun. [score:1]
miR-127 Represses HCC Cell Migration Induced by MMP13. [score:1]
c-Jun also antagonizes p53 activation of the miR-127 promoter and gene transcription. [score:1]
The 97HLuc-Sico and 97HLuc-miR-127 cells were used in Xenograft mouse mo del. [score:1]
Both flanks of each mouse were injected with 0.5×10 [6] 97HLuc-Sico or 97HLuc-miR-127 cells mixed with Matrigel (Invitrogen) in a total volume of 100 µl. [score:1]
MiR-127 is clustered with miR-433 and both miRNA primary transcripts are controlled by nuclear receptor signaling involving small heterodimer partner (SHP) and estrogen related receptor gamma (ERRγ) [2]– [4]. [score:1]
Overexpression of miR-127 decreased the migration rate of MHCC97H by about 40% as examined by a wound healing assay (Fig. 1A), as well as by an alternate Transwell cell migration assay (Fig. 1B, left two). [score:1]
The levels of miR-127 were significantly reduced in HepG2 cells transfected with p53-siRNA (Fig. 4E, left and middle). [score:1]
Thus far, the in vivo physiological function of miR-127 has not been studied and remains largely unknown. [score:1]
In particular, conflicting information is available regarding the potential role of miR-127 in human cancers. [score:1]
TGFβ enhances c-Jun -mediated repression of miR-127 via ERK and JNK pathways. [score:1]
Control 97HLuc-Sico or 97HLuc-miR-127 cells were grafted subcutaneously in the dorsa of athymic mice, and tumor growth was monitored using the Xenogen bioluminescent imaging system by day 9. The number represents tumor images detected (photons/s/cm [2]/steridian). [score:1]
We next examined the effects of miR-127 and MMP13 on HCC cell migration. [score:1]
It would be interesting to determine in future studies whether miR-127 may play a role in TGFβ -mediated Smad activity. [score:1]
Overall, the results suggest that p53 activation of miR-127 is a common but not a cell type specific phenomenon. [score:1]
Ad-cre virus (100 PFU) was then used to infect 97HLuc-SicoGFP or 97HLuc-miR-127GFP cells, which removed the GFP marker and generated 97HLuc-Sico and 97HLuc-miR-127 cells, respectively. [score:1]
Both 97HLuc-Sico and 97HLuc-miR-127 cells were implanted subcutaneously in nude mice and tumor growth was monitored using the Xenogen bioluminescent imaging system [14]. [score:1]
On the other hand, p38 protein kinases, another downstream mediator of the mitogen-activated protein kinase pathways [35], is not involved in TGFβ activation of c-Jun, but is involved in TGFβ repression of miR-127. [score:1]
Despite these existing literature reports pointing to a role for miR-127 in various cancers, no detailed functional and mechanistic studies have been done. [score:1]
The levels of miR-127 were not affected by MMP13 (Fig. 3C). [score:1]
0065256.g002 Figure 2(A) Sequence alignment between miR-127 and the 3′UTR of MMP13 in human, mouse, and rat. [score:1]
Hela cells were co -transfected with miR-127 or AP1 promoter reporter along with c-Jun/c-Fos plasmid (100 ng) in the absence or presence of TGFβ (5 ng/ml). [score:1]
miR-127 attenuates TGFβ -mediated induction of HCC cell migration. [score:1]
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[+] score: 217
Alteration of those miRNAs expression may in turn affect the expression of the imprinted genes, as evidenced by the down-regulation of Rtl1 by miR-127 in this study. [score:8]
Thus, the expression of human miR-127 was ∼20 times higher than human miR-433, the expression of rat miR-127 was ∼47 times higher than rat miR-433, and the expression of dog miR-127 was ∼40 times higher than dog miR-433. [score:7]
Down-Regulation of the Imprinted Gene Rtl1 by Overexpression of miR-127. [score:6]
This data suggests that miR-127 may function as a siRNA to down-regulate its host gene expression. [score:6]
Potential PCR amplification from genomic DNA contamination was eliminated by treating the total RNA with DNase I. As shown in Figures 6a–c, primary transcripts of the human (a), rat (b), or dog (c) miR-433 and miR-127 were easily detected in cells that over-expressed the recombinant expression vector, respectively. [score:5]
0007829.g005 Figure 5(a) The miR-433/127 loci expression plasmid of human, rat, or dog was expressed in mouse Hepa-1 cells (different species), and the binding of ERRγ to the endogenous promoter of miR-433 and of miR-127 of each species was detected using specific ERRγ antibodies. [score:5]
0007829.g006 Figure 6(Panels a–c) Semi-quantitative RT-PCR analysis of pri-miR-433 and pri-miR-127 expression transcribed from the human (a), rat (b), and dog (c) miR-433/127 loci expression plasmid. [score:5]
The recombinant human, rat, or dog miR-433/127 loci expression vector (designated pMIR-REPORT-NoMp-human, rat or dog) was then transfected into Hepa-1 cells and the expression of miR-433 and miR-127 primary transcripts was examined using semi-quantitative RT-PCR. [score:5]
Because miR-127 is located in an imprinted region encoding Rtl1, we determined if changes in miR-127 expression would affect the expression of Rtl1. [score:5]
Artificial Expression of miR-433 and miR-127 In Vitro in CellsOur previous studies showed that the mouse miR-433 and miR-127 genes overlapped and the expression of mouse miR-433 and miR-127 was controlled by independent promoters [3], [4]. [score:5]
0007829.g007 Figure 7 The expression vector of miR-127 was transfected in human Hela and mouse Hepa-1 cells and the expression of Rtl1 was determined by a modified strand-specific q-PCR. [score:5]
Similarly, the rat miR-433 and miR-127 was ∼210 fold and ∼10000 fold ovexpressed (Figure 6f) and the dog miR-433 and miR-127 was ∼4 fold and ∼160 fold ovexpressed (Figure 6g), respectively. [score:5]
The expression vector of miR-127 was transfected in human Hela and mouse Hepa-1 cells and the expression of Rtl1 was determined by a modified strand-specific q-PCR. [score:5]
We overexpressed miR-127 in human Hela and mouse Hepa-1 cells using an expression vector of miR-127 and the level of Rtl1 was assessed using a strand specific q-PCR analysis. [score:5]
For instance, if mutations occurred in the region between pre-miR-433 and pre-miR-127, it would be likely to affect both the processing of mature miR-433 and the regulation of miR-127 expression. [score:5]
We next determined expression levels of the mature miR-433 and miR-127 in Hepa-1 cells after recombinant vector over -expression. [score:5]
Interestingly, ectopic expression of miR-127 resulted in a significant reduction in Rtl1 expression in both cells (Figure 7). [score:5]
Based on this information, we made a direct comparison between the expression level of miR-433 and miR-127. [score:4]
Compared with non-vector transfected cells, the human miR-433 was ∼100 fold over-expressed whereas the human miR-127 was ∼2000 fold over-expressed (Figure 6e). [score:4]
The imprinted expression of miR-127 has been shown to undergo DNA methylation regulation in mouse embryos [26] and cancer cells [27]. [score:4]
Our studies provide evidence for a conserved gene structure and ERR/SHP dependent regulation of miR-433 and miR-127 gene expression in mammals. [score:4]
We recently have shown that gene expression of miR-433 and miR-127 in mice was regulated via a nuclear receptor ERRγ/SHP dependent mechanism [4]. [score:4]
Based on the identification of the same binding motifs, we predicted that a common regulatory mechanism of miR-433 and miR-127 expression may exist among different mammalian species. [score:4]
Artificial Expression of miR-433 and miR-127 In Vitro in Cells. [score:3]
Due to high expression of primary transcript of miR-433 and mIR-127, different PCR cycles were used (see Figure 6). [score:3]
This would allow us to determine if the transcriptional expression of miR-433 or miR-127 could be driven by its own promoter from the endogenous miR-433/127 loci. [score:3]
The mouse cell line Hepa1 and human cell line Hela were transfected with miR-127 expression vector. [score:3]
On the other hand, we observed a common transcriptional mechanism governing the expression of miR-433 and miR-127 in mammals, which involved ERR family members and orphan receptor SHP. [score:3]
As expected, ERRγ dose -dependently activated promoters of miR-433 and miR-127 of human (Figure 4a), rat (Figure 4b), and dog (Figure 4c), which was repressed by co -expression of SHP. [score:3]
Transcriptional expression of miR-433 and miR-127 from the miR-433/127 loci in human, rat, and dog. [score:3]
In addition, the expression level of pri-miR-433 was markedly lower than that of pri-miR-127 (Figure 6d) in all three species, suggesting pri-miR-433 and pri-miR-127 were transcribed differentially from an independent transcription unit. [score:3]
These differential expression results provided further evidence that miR-433 and miR-127 produced from the miR-433-127 loci were transcribed from two separate promoters in human, rat, and dog. [score:3]
Our previous studies showed that the mouse miR-433 and miR-127 genes overlapped and the expression of mouse miR-433 and miR-127 was controlled by independent promoters [3], [4]. [score:3]
In order to avoid the effect of endogenous miR-127 and miR-433 primary transcripts in Hela cells, we overexpressed the pMIR-Report human433/127 loci, pMIR-Report rat433/127 loci, and pMIR-Report dog433/127 loci in Hepa1 cells. [score:3]
The expression level of primary transcript of miR-433 and miR-127 was determined by semi-quantitative PCR using primers listed in Supplementary Material Table S3. [score:2]
We recently have reported that the full length primary transcripts of mouse miR-433 and miR-127 overlapped in a 5′–3′ unidirectional way [3]. [score:2]
We elucidated a common regulatory mechanism governing miR-433 and miR-127 promoter activities, which was dependent on nuclear receptor estrogen related receptor gamma (ERRγ, NR3B3) and small heterodimer partner (SHP, NR0B2) [4]. [score:2]
In this study, we used pMIR-Report-human 433/127, pMIR-Report-rat433/127, pMIR-Report-dog433/127 plasmids as the standard template to determine the PCR efficiency, then compared the expression level of miR-433 and miR-127 primary transcripts. [score:2]
The conservation of the transcriptional regulation of miR-433 and miR-127 further supports the notion that the miR-433/127 loci in mammals might be evolved from an ancient common origin. [score:2]
Primers used to determine the expression of primary transcripts of miR-433 and of miR-127 are located surrounding the precursors of miR-433 and of miR-127. [score:2]
In conclusion, our studies for the first time provide evidence for a conserved structure and transcriptional regulation of the clustered miR-433 and miR-127 genes in mammals, including humans. [score:2]
However, the question remains to be determined whether molecular details of miR-433 and miR-127 regulation by ERR/SHP are restricted to mouse or whether they apply to other species. [score:2]
Common Regulation of miR-433 and miR-127 Promoter Activity among Mammalian Species. [score:2]
Our published results showed that miR-433 and miR-127 genes are overlapped in a 5′–3′ unidirectional way in mouse [3] and these two non-coding genes have an antisense transcript, RTL1 [19]. [score:2]
Based on their overlapping gene structure and transcriptional initiation and termination sites, we subsequently cloned promoters of miR-433 and miR-127. [score:1]
ERRγ was co-immunoprecipitated on the ERRE containing the endogenous promoter regions of miR-433 and miR-127 in the liver of human and rat, and dog spleen, respectively (Figure 5b). [score:1]
Although the miR-433/127 loci were located on different chromosomes (Chr) in those species (human, Chr 14; Chimpanzee, Chr14; Horse, Chr 24; Dog, Chr 8; Monkey, Chr 7; Rat, Chr 6; Cow, Chr 21; mouse, Chr 12), multiple sequence alignment (MSA) of the precursors, pre-miR-433 and pre-miR-127, showed that the sequence similarity of pre-miR-433 hairpins was ∼95% (Figure 1a) and of pre-miR-127 was 100% (Figure 1b) among those species. [score:1]
To determine if miR-433 and miR-127 in human, rat, and dog can be independently and differentially transcribed using each miRNA's own promoter, we cloned a large (∼4.5 kb) human, rat, or dog genomic DNA fragment containing miR-433 and miR-127 and their promoter regions into pMIR-REPORT vector (Figure S2). [score:1]
Figure S1 Transient transfection assays to determine ERRα and ERRβ regulation of miR-433 and miR-127 promoter (pro. ) [score:1]
Transient transfection assays to determine ERRγ and SHP regulation of miR-433 and miR-127 promoter (pro. ) [score:1]
MatInspector of Genomatix Software Suite was used to predict the transcription factor binding sites in the promoter regions of miR-433 and miR-127 in different species, which was completely using Default parameters (http://www. [score:1]
0007829.g004 Figure 4Transient transfection assays to determine ERRγ and SHP regulation of miR-433 and miR-127 promoter (pro. ) [score:1]
The mature sequences of miR-433 and miR-127 were identical among the eight species. [score:1]
The response elements of the miR-433 and miR-127 genes from eight different species are illustrated. [score:1]
As shown in Figure 5, ERRγ was found to Co-IP on both the miR-433 and miR-127 promoters of human, rat, or dog. [score:1]
This resulted in the cloning of the gene cluster encoding mouse miR-433 and miR-127, which provided the first report for an overlapping code usage of the paired miR-433/127 gene [3]. [score:1]
The promoters of pri-miR-433 and pri-miR-127 were cloned into a pGL3-basic vector, respectively. [score:1]
ERRa, but not ERRβ, showed strong activation of miR-433 and miR-127 promoters of human, rat, and dog (Figure S1). [score:1]
The distance between miR-433 and miR-127 showed a striking similarity: 986 bp in human, chimpanzee, horse, dog, and monkey, 989 bp in rat, 988 bp in cow, and 1007 bp in mouse. [score:1]
The promoter of pri-miR-433 and of pri-miR-127 from each species was cloned into a pGL3-basic vector, respectively. [score:1]
Our results presented in this study provide evidence that the miR-433 and miR-127 overlapping genes have a higher rate of conservation in mammalian species. [score:1]
The genomic region between the two pre-miRNAs is predicted to function as the promoter of miR-127 based on our published mouse data [4]. [score:1]
BLASTN search of genome sequences of different species was completed online and a 5 kb genomic sequence surrounding the miR-433 and miR-127 precursors in each species was extracted manually. [score:1]
ChIP analysis of ERRγ Co-immunoprecipitation (Co-IP) on the miR-433 and miR-127 promoter region containing putative ERRE in human, rat, and dog. [score:1]
The precursor sequences of miR-433 and miR-127 were downloaded from the Sanger Institute (http://microrna. [score:1]
MSA of miR-433 and miR-127 gene promoters in eight mammalian species. [score:1]
Using mouse miR-433 and miR-127 precursor hairpin structure sequences as a query, we searched the genome databases of seven other species, including human, chimpanzee, horse, dog, monkey, rat, and cow. [score:1]
The promoters of miR-433 and miR-127 from human, rat and dog were cloned into a pGL3 basic vector, respectively. [score:1]
Although the miR-433/127 gene loci was located on different chromosomes in different species, the distance between miR-433 and miR-127 is very similar, which is ∼1 kb. [score:1]
The 4.5 kb genomic sequences centered miR-433 and miR-127 were extracted. [score:1]
Representative common TF binding motifs (1°∼4°) are shown, and their positions appear to be conserved in the promoter region of miR-433 and of miR-127 among different species. [score:1]
Predicted ERRE sites on the miR-433 and miR-127 gene promoters. [score:1]
Promoter analysis of miR-433 and miR-127 luciferase reporters of human, rat and dog. [score:1]
Why is the miR-433 and miR-127 overlapping gene structure in mammalian species so conserved? [score:1]
0007829.g003 Figure 3 The response elements of the miR-433 and miR-127 genes from eight different species are illustrated. [score:1]
Conserved Transcription Factor Binding Motifs in the Upstream Region of miR-433 and of miR-127 among Mammalian Species. [score:1]
Finally, the long DNA fragments containing human, rat or dog miR-433 and miR-127 loci were inserted into Asc I and Pac I sites of pMIR-REPORT-NoMp. [score:1]
We used MatInspector of Genomatix Software Suite to identify transcription factor binding motifs and position preference in the upstream promoter regions of miR-433 and of miR-127 in eight mammalian species. [score:1]
We found that miR-433 and miR-127 had almost identical PCR amplification efficiency (Supplementary Material Table S4). [score:1]
Conserved response elements in the promoters of miR-433 and miR-127 of eight mammalian species. [score:1]
Semi-Quantitative RT-PCR for miR-433 and miR-127 Primary Transcripts. [score:1]
Based on the above gene structure analysis and sequence prediction referenced from our published mouse data [3], [4], we hypothesized that the genomic location of promoters of miR-433 and miR-127 was similar in other mammalian species as in mouse. [score:1]
In the present study, we analyzed genes encoding miR-433 and miR-127 and determined the promoter transactivation of miR-433 and miR-127 from other mammalian species, including humans. [score:1]
To further confirm this result, the direct association of ERRγ with miR-433 and miR-127 promoters of each species in vivo was assessed using ChIP assays. [score:1]
The lowest evolutionary distance between cow and other species is 0.10114 and the sequence homology is low, based on the sequence alignment of the miR-127 promoter region (Figure 2b). [score:1]
miR-127 pro. [score:1]
The sequence similarity in either the miR-433 promoter region (Figure 2a) or the genomic region between pre-miR-433 and pre-miR-127 (Figure 2b) was low among the eight species. [score:1]
We cloned the promoters of miR-433 and miR-127 into pGL3 luciferase reporters using genomic DNAs isolated from liver specimens of human, rat and dog. [score:1]
The conservation of pre-miR-433 and pre-miR-127 hairpin sequences as well as the distance between them among different mammalian species raised the possibility that miR-433 and miR-127 might be evolved from the same DNA origin during evolution. [score:1]
Multiple sequence alignment (MSA) of miR-433 and miR-127 precursor hairpin sequences in eight mammalian species. [score:1]
Despite lower sequence similarity, analysis of miR-433 and miR-127 promoters of those species predicted common nuclear receptor binding sites, including ERRE (Figure 3 and Table 1). [score:1]
Unique potential binding motifs were also identified in the promoter region of miR-433 and of miR-127 in each species. [score:1]
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3
[+] score: 165
Other miRNAs from this paper: hsa-mir-127
It has been reported that BCL6 (B-cell CLL/lymphoma 6) is an miR-127 target in cancer cells 13, 23, 31 whose expression is upregulated during myogenic differentiation in C2C12 cells, [32] suggesting that miR-127 might promote myogenic differentiation by targeting BCL6. [score:10]
However, our data did not support this possibility, as evidenced by the observations that BCL6 mRNA levels were not reduced in miR-127-OE muscle (Figure 4a) and expression of the BCL6 gene was upregulated during C2C12 cell differentiation (Figure 4b), an expression pattern similar to that of miR-127 (Figure 1b). [score:8]
Mechanistically, we further provide evidence that miR-127 enhances SC differentiation by directly targeting the gene encoding S1PR3, a G-protein-coupled receptor for the bioactive sphingolipid S1P (sphingosine-1-phosphate), which is an important regulator of skeletal muscle function. [score:5]
Interestingly, miR-127 was significantly upregulated in response to the induction of myogenic differentiation in both the C2C12 mouse myoblast cell line (Figure 1b and Supplementary Figure S1) and primary mouse myoblasts (Figure 1c) as reported very recently, [27] indicating a functional role of miR-127 in regulating myogenic cell differentiation. [score:5]
These findings suggest that miR-127 may be a potential therapeutic target in the treatment of human muscular diseases. [score:5]
11, 33 S1PR3, which contains a putative miR-127 binding site in its 3′-untranslated region (3′-UTR) (Figure 4c), was ranked 75 out of more than 10 000 targets of miR-127 predicted by the analysis tool, miRWalk. [score:5]
11, 33 S1PR3, which contains a putative miR-127 binding site in its 3′-untranslated region (3′-UTR) (Figure 4c), was ranked 75 out of more than 10 000 targets of miR-127 predicted by the analysis tool, miRWalk. [score:5]
[33] To confirm directly the functional correlation between miR-127 and S1PR3, we overexpressed S1PR3 in C2C12 cells stably OE miR-127 (Figure 6a). [score:4]
Consistent with this, both mRNA (Figure 4f) and protein (Figure 4g) levels of S1PR3 were also lower in the skeletal muscle of miR-127 TG mice than WT mice, indicating that miR-127 directly targets SIPR3 both in vitro and in vivo. [score:4]
[33] Interestingly, we found that the expression pattern of endogenous S1PR3 during muscle regeneration (Figure 4h) was opposite that of miR-127 (Figure 4i), suggesting that miR-127 regulates myogenic differentiation by modulating S1PR3 function. [score:4]
These results indicate that miR-127 directly targets S1PR3. [score:4]
Collectively, these results demonstrate that miR-127 functionally regulates myogenic differentiation by targeting S1PR3. [score:4]
We then further predicted functional targets of miR-127 using computational and bioinformatics -based approaches. [score:3]
miR-127 was overexpressed ~4.5-fold in the skeletal muscle of mdx;miR-127 mice (Figure 7a). [score:3]
Overexpression of miR-127 in the TG mice was driven by the β-actin promoter (pCAGGS). [score:3]
To experimentally validate that S1PR3 is a target of miR-127, we generated luciferase reporter constructs carrying the 3′-UTR sequence of WT S1PR3 (WT-UTR) and a mutant form (mut-3′-UTR) harboring substitutions in the miR-127 binding sites in the 3′-UTR. [score:3]
29, 30 Although miR-127 expression in the skeletal muscle was increased 2.5-fold in the F line (Figure 2a) and 14-fold in the C line (Figure 2b), we did not observe significant difference in bodyweight (Figure 2c), muscle mass (Figure 2d) or fiber size (Figures 2e and f) between either line miR-127 TG mice and wild-type (WT) mice at the indicated ages. [score:3]
Among the predicted miR-127 targets, S1PR3 (sphingosine-1-phosphate receptor 3) seemed particularly interesting because of its previously reported roles in muscle differentiation and regeneration. [score:3]
Taken together, our data indicate that miR-127 overexpression significantly reduces the dystrophic muscle pathology in mdx mice by improving sarcolemmal integrity, despite the absence of obvious alterations in the cross-sectional area of myofibers in mdx;miR-127 mice (Figure 7h). [score:3]
miR-127 augments myogenic differentiation by targeting S1PR3. [score:3]
As shown in Figure 1a and consistent with published data, 26, 27 we found that miR-127 is predominantly expressed in the skeletal muscle and the brain. [score:3]
Similar effects were also observed for MHC immunoreactivity (Figure 6e), fusion index (Figure 6f) and levels of MHC mRNA (Figure 6g), demonstrating that S1PR3 overexpression abolishes the miR-127 -mediated enhancement of muscle cell differentiation. [score:3]
Taken together, these findings show that miR-127 overexpression morphologically and functionally improves the dystrophic phenotype of mdx mice. [score:3]
To further establish a functional link between miR-127 and S1PR3, we first examined the expression of endogenous S1PR3 in miR-127 OE C2C12 cells and in thr skeletal muscle of miR-127 TG mice. [score:3]
[33] In this report, we identified S1PR3 as a functional target of miR-127. [score:3]
As expected, miR-127 expression was higher in primary myoblasts isolated from miR-127 TG mice than in those from WT mice (Figure 3f). [score:3]
Very recently, Li et al. [27] described a dynamic expression of miRNA-127-3p in proliferating and differentiating C2C12 cells as we reported here. [score:3]
To overexpress S1PR3, miR-127-stable cell or control cells were transfected with 1.6 ng pcDNA 3.0-S1PR3 plasmids per 12-plate well by using the FuGene HD transfection reagent (Roche, Basel, Switzerland). [score:3]
Overexpression of S1PR3 significantly blocked miR-127 -mediated myogenic differentiation. [score:3]
For this purpose, we generated two miR-127 TG mice lines (C line and F line), in which miR-127 overexpression was driven by the β-actin promoter. [score:3]
Notably, overexpression of miR-127 also considerably improved the muscular dystrophy phenotype in mdx mice by enhancing SC differentiation. [score:3]
Moreover, miR-127 overexpression significantly ameliorates muscular dystrophy symptoms in mdx mice. [score:3]
The expression of miR-127 was ~25-fold higher in miR-127 OE cells compared with that in NC cells (Figure 1d). [score:2]
To investigate directly the impact of miR-127 on myogenic cell differentiation, we established C2C12 cell lines stably overexpressing (OE) miR-127 or the empty vector as a negative control (NC). [score:2]
The expression levels of mature miRNAs miR-127-3p were determined using the miRNA-specific TaqMan microRNA Assay Kit (Applied Biosystems, CA, USA), U6 was used as a normalizer. [score:2]
C2C12 cell lines stably OE miR-127 were established by infection with lentivirus containing H1-miR-127-CMV-puromycin (Genechem, Shanghai, China). [score:1]
miR-127 transgenic mice in a C57BL/6 background were generated by the Mo del Animal Research Center of Nanjing University. [score:1]
These results indicate that miR-127 significantly potentiates myogenic cell differentiation in vitro. [score:1]
To this end, we generated mdx mice OE miR-127 (mdx;miR-127) and used them to assess the ability of miR-127 to alleviate symptoms of muscular dystrophy. [score:1]
Next, we assessed the functional role of miR-127 in mediating skeletal muscle regeneration. [score:1]
MyoG [+] cells were less numerous among C2C12 cells OE both miR-127 and S1PR3 (Figures 6b and c), and the level of MyoG mRNA in these cells was lower than that in cells stably OE only miR-127 (Figure 6d). [score:1]
As shown in Figure 4d, co-transfection of miR-127 mimics decreased the luciferase activity of WT-UTR, but not that of mut-3′-UTR. [score:1]
Immunostaining for the early myogenic differentiation marker myogenin (MyoG) revealed significantly increased the number of differentiating cells in miR-127 OE cultures than in NC cultures following induction of differentiation (Figures 1e and f). [score:1]
miR-127 attenuates the dystrophic phenotype of mdx miceGiven that miR-127 accelerates muscle regeneration in mice, we reasoned that miR-127 might reduce the muscular dystrophy phenotype in mdx mice. [score:1]
miR-127-3p probes were labeled with γ- [32]P-ATP using T4 DNA kinase (Fermentas, Thermo Scientific, Waltham, MA, USA). [score:1]
Cells plated in 24-well plates were co -transfected with pGL3-S1PR3-3′-UTR and miR-127 mimics (triplicates for each transfection). [score:1]
The control pGL-3 construct was insensitive to miR-127. [score:1]
The functional role of miR-127 in promoting myogenic cell differentiation was further validated using primary myoblasts isolated from hindlimb skeletal muscles of miR-127 TG and WT mice. [score:1]
Notably, the running time of mdx;miR-127 mice was remarkably longer than that of mdx mice (Figure 7i). [score:1]
miR-127 attenuates the dystrophic phenotype of mdx mice. [score:1]
The ability of miR-127 to enhance C2C12 cell differentiation in vitro prompted us to investigate its functional role in regulating skeletal muscle development and regeneration in vivo. [score:1]
Taken together, these findings reveal a significant role of miR-127 in promoting myogenic differentiation, both in vitro and in vivo. [score:1]
Consistent with the MyoG staining results, levels of MyoG mRNA (Figure 1g) and protein (Figure 1h) were also significantly increased in miR-127 OE cells relative to NC cells. [score:1]
To this end, we injured tibialis anterior (TA) muscles from miR-127 TG and WT mice using cardiotoxin (CTX) as described previously. [score:1]
[16] To assess directly the functional role of miR-127 in regulating SC differentiation during regeneration, we measured the size of regenerating myofibers 7.5 days postinjury. [score:1]
The ability of miR-127 to stimulate C2C12 cell differentiation is further supported by the observed increase in myosin heavy chain (MHC) immunoreactivity (Figure 1i) and fusion index (Figure 1j), and higher levels of MHC mRNA (Figure 1k) and protein (Figure 1l) in miR-127 OE cells. [score:1]
Given that miR-127 accelerates muscle regeneration in mice, we reasoned that miR-127 might reduce the muscular dystrophy phenotype in mdx mice. [score:1]
mdx;miR-127 mice were generated by breeding miR-127 transgenic male mice with homozygous mdx/mdx female mice. [score:1]
Interestingly, levels of serum CK were significantly lower in mdx;miR-127 mice than in mdx mice (Figure 7c). [score:1]
miR-127 enhances C2C12 cell differentiation. [score:1]
EDL muscles from mdx;miR-127 mice exhibited a greater peak twitch force (Figure 7j) and a 1.5-fold increase in the peak tetanic force (Figure 7k) than those from mdx mice. [score:1]
[39] Therefore, modulating the levels of the metabolite, S1P, or manipulating its receptor, S1PR3, by miR-127 would represent a potential therapeutic strategy for muscular dystrophy. [score:1]
Collectively, this morphological and molecular evidence revealed that myogenic differentiation was significantly accelerated in miR-127 TG mice undergoing muscle regeneration. [score:1]
miR-127 accelerates skeletal muscle regeneration by promoting SC differentiation. [score:1]
In the context of CTX -induced muscle regeneration, miR-127 transgenic mice exhibited a phenotype similar to that observed in S1PR3 -null mice. [score:1]
As a consequence, S1PR3 mRNA levels were significantly reduced in the skeletal muscle of mdx;miR-127 mice relative to those in mdx mice (Figure 7b). [score:1]
We found that S1PR3 mRNA levels were decreased in miR-127 OE cells (Figure 4e). [score:1]
Additionally, we found no significant difference in Pax7 -positive (Pax7 [+]) SC numbers between WT and miR-127 TG mice (Figures 2g and h). [score:1]
The gender- and age-matched littermates of the miR-127 TG and WT mice were used for all phenotypic analysis throughout the study. [score:1]
Next, we investigated the molecular mechanism underlying the function of miR-127 in promoting myogenic cell differentiation by identifying its targets. [score:1]
Using transgenic mouse mo dels in this study, we further demonstrate that miR-127 accelerates skeletal muscle regeneration in mice. [score:1]
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4
[+] score: 115
Consistently, VSV -induced Bcl6 expression was remarkably down-regulated by miR-127 overexpression but elevated by miR-127 inhibition (Fig. 5d). [score:10]
The expression of proinflammatory cytokines IL-6 and TNF-α, however, was suppressed upon miR-127 overexpression and increased by miR-127 blocking (Fig. 6c,f). [score:7]
In support of this, ectopic miR-127 expression showed to significantly enhance VSV-triggered IRF7 transcription, as well as the expression of IFNβ and ISG15. [score:5]
The expression of miR-127 likely paralleled to IFNβ production while correlating inversely with Bcl6 expression (Fig. 1a,b). [score:5]
Indeed, the induction of miR-127 upon VSV infection, parallel to its inhibition of Bcl6 expression, led to a disengagement of the co-repressors, NcoR2 and HDAC3 from the IRF7 gene promoter (Fig. 5g). [score:5]
In contrast, inhibition of miR-127 expression kept these antiviral genes in check (Fig. 5e,f). [score:5]
Enforced expression of miR-127 however further promoted the clearance of the Bcl6 co-repressors, whereas miR-127 inhibitors augmented the binding of Bcl6, NcoR2 and HDAC3 to the IRF7 promoter site. [score:5]
Notably, although NcoR2 and HDAC3 remained at a high level over the infection period, they failed to reside on IRF7 promoter and hinder its transcription when Bcl6 expression was suppressed by miR-127. [score:5]
The data further confirmed that miR-127 exerted its regulatory effect by specifically acting on Bcl6 and the associated co -inhibitory complex. [score:4]
A signal -dependent induction of miR-127, mostly through down-regulation of Bcl6, led to the disassembly of the co-repressive complex and thereby facilitated the signaling activation (Fig. 5k). [score:4]
Thus, miR-127 and Bcl6 exert a fine-tuning effect on antiviral innate immunity and thus have a profound impact on virus -associated diseases (Fig. 5k). [score:3]
Importantly, we demonstrated that the protection conveyed by miR-127 was closely related with its ability to repress Bcl6 expression and thus enhance IRF7 gene (Fig. 6h,i). [score:3]
Consistently, IFNβ level in BALF was raised by miR-127 treatment but repressed upon miR-127 inhibition (Fig. 6b,e). [score:3]
Also, we found that VSV -induced miR-127 expression was severely impaired upon the loss of NF-κB or IFN, the two key factors for antiviral signaling amplification (Fig. 5b and supplementary Fig. 2), implying the involvement of the miR-127/Bcl6 axis in RIG-I signaling. [score:3]
This may lead to the assumption that the small amount of type I IFN produced in resting or initially activated cells is able to promote miR-127 expression, which in turn enhance antiviral signaling by removing Bcl6 -mediated IRF7 repression. [score:3]
More strikingly, when we used RI-BPI to block the interplay between Bcl6 and NcoR2, the enhanced restraint on IRF7 transcription caused by miR-127 antimir was largely abrogated, as evidenced by the restoration of IRF7 and IFNβ expression, and accordingly, the decreased viral burden (Fig. 5h–j). [score:3]
Tight control of miR-127 expression is thus essential to restrain antiviral signaling in resting or temporarily activated macrophages. [score:3]
On the other hand, our data revealed that miR-127 exerted an unexpectedly inhibitory role on NF-κB activation, which, combined with the observed NF-κB -dependent miR-127 generation, constitutes a negative feedback mechanism to control overzealous antiviral gene activation. [score:3]
Interestingly, we reported in a previous study that VSV can trigger a prominent induction of miR-127, a miRNA molecule that has been implicated in Bcl6 -mediated cancer development and other pathophysiology 23 31. [score:2]
The miR-127-Bcl6-IRF7 circuit regulates the viral immunopathologic response in vivo. [score:2]
Taken together, the miR-127/Bcl6 axis constituted dynamic regulatory machinery during antiviral response. [score:2]
In the search of the molecular bridge that delivered the viral information to the Bcl6 regulation, we identify miR-127, a RIG-I-inducible miRNA, as a strong candidate. [score:2]
Interestingly, we noted that treatment of macrophages with miR-127 mimic or antimir led to a marked decrease or increase respectively in the transcription of pro-inflammatory cytokines (supplementary Fig. 3a,b), consistent with the regulatory role for Bcl6 in inflammatory signaling we described above. [score:2]
Next, given the above finding that the Bcl6 co-repressor played a pivotal role in IRF7 -driven antiviral signaling, we then wondered if miR-127 would participate in this regulatory mode in the course of viral infection. [score:2]
These data thus suggested that miR-127 was essential for the Bcl6 -mediated transcription regulation and chromatin remo deling that was essential for antiviral response. [score:2]
Because the potential sequence bound by miR-127 has been previously identified at the 3′UTR of the Bcl6 gene 23, we then tested its direct effect on Bcl6 using a reporter plasmid containing the predicted sequence. [score:2]
The in vivo function of the miR-127/Bcl6/IRF7 regulatory circuit. [score:2]
miR-127 mediates the signal -dependent turnover of Bcl6 coregulator. [score:2]
Signal -dependent clearance of the Bcl6, largely dependent on the miR-127 induction, led to the optimal activation of antiviral signaling and the alleviated inflammatory response. [score:1]
Additionally, miR-127 was found to be induced by viral infection, such as EBV and HBV infection, and was implicated in Burkitt lymphoma pathogenesis 39. [score:1]
The data suggest a potential role for miR-127 in host-virus interaction. [score:1]
In fact, the current study demonstrated that, following a transient repression, miR-127 was rapidly induced upon stimulation of intracellular poly I:C or VSV (Fig. 5a). [score:1]
The results indicated that the activity of reporter plasmid containing the intact Bcl6 3′UTR was significantly repressed by miR-127 mimic but enhanced by its antimir (Fig. 5c). [score:1]
C57BL/6 mice (n = 4 per group) were pretreated with miR-127, anti-miR-127 or their non-specific controls for 24 h and then infected with VSV (2 × 10 [7] pfu per mouse). [score:1]
Moreover, our data demonstrated a critical requirement of IFNβ and NF-κB activity in the induction of miR-127 upon viral infection. [score:1]
Strikingly, pretreatment of mice with a miR-127 mimic, but not a scrambled control, significantly reduced viral loads in their lungs, in terms of viral titer and viral mRNA levels. [score:1]
The data thus implied an involvement of miR-127/Bcl6 axis in antiviral responses. [score:1]
MiR-127 mediates signal -dependent turnover of the Bcl6 co-regulator. [score:1]
Together, our data demonstrated a prominent and specific role of the miR-127/Bcl6/IRF7 loop in the host innate immunity against viral infection. [score:1]
In contrast, anti-miR-127 administration caused a profound elevation in the viral burden (Fig. 6a,d). [score:1]
For miR-127 functional analysis, the mice were instilled with miR-127 mimic, anti-miR-127 or their non-specific oligonucleotide controls (2 mg kg [−1], i. t. ) for 24 h, and then challenged with VSV. [score:1]
Congruent with this, a substantial decrease in inflammatory cell infiltration and debris deposition was observed in miR-127 -treated mice, whereas exaggerated inflammatory pathology was generated in the animals receiving miR-127 antimir (Fig. 6g). [score:1]
Alternatively, RAW264.7 cells were transfected with miR-127, anti-miR-127 or the non-specific control (NC) for 24 h and then infected with VSV for the indicated time periods. [score:1]
Furthermore, we identify a miR-127 -mediated molecular switch that, by modulation of the Bcl6 level and the subsequent assembly of the co-repressor complex, reprogrammed the IRF7 gene from a “locked” to an active state and thus initiated RIG-I -driven signaling. [score:1]
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5
[+] score: 76
Ssc-miR-103 and ssc-miR-107 expression was slightly lower in premolars (Dpm) than in other types of teeth, ssc-miR-133a and ssc-miR-133b expression was much higher in Dpm than in other types of teeth, and ssc-miR-127 expression gradually increased from the incisor (Di) to the molar (Dm)In order to detect the oral developmental specificity of the five selected miRNAs, we further extracted kidney, liver and submandibular gland to contrast the five miRNAs expression (Fig.   5). [score:10]
Ssc-miR-103 and ssc-miR-107 expression was slightly lower in premolars (Dpm) than in other types of teeth, ssc-miR-133a and ssc-miR-133b expression was much higher in Dpm than in other types of teeth, and ssc-miR-127 expression gradually increased from the incisor (Di) to the molar (Dm) In order to detect the oral developmental specificity of the five selected miRNAs, we further extracted kidney, liver and submandibular gland to contrast the five miRNAs expression (Fig.   5). [score:10]
At E50, miR-127 expression in all four types of teeth stayed almost the same, but expression in the premolar was not observed and the expression level was lower and more restricted in the inner enamel epithelium of the molar (E1–E4). [score:7]
We also found that expression levels of ssc-miR-103 and ssc-miR-107 were slightly lower in Dpm than in other types of teeth, ssc-miR-133 a and ssc-miR-133b expression levels were much higher in Dpm than in other types of teeth, and ssc-miR-127 expression increased in Di, Dc, Dpm, and Dm, in that order. [score:7]
At E60, mir-127 expression in the incisor, canine, and premolar increased, while expression decreased in the molar. [score:5]
d Seed sequences and duplexes (boxes) of five isomiR families including 11 miRNAs had high-signal (signal ≥500) miRNA transcripts based on cluster analyses of miRNA expression patterns, thus identifying them as key microRNAs After performing six pairwise comparisons among the subgroups, we added another candidate miRNA, miR-127, which was significantly differentially expressed among Di, Dc, and Dpm (Fig.   3b– c). [score:5]
d Seed sequences and duplexes (boxes) of five isomiR families including 11 miRNAs had high-signal (signal ≥500) miRNA transcripts based on cluster analyses of miRNA expression patterns, thus identifying them as key microRNAsAfter performing six pairwise comparisons among the subgroups, we added another candidate miRNA, miR-127, which was significantly differentially expressed among Di, Dc, and Dpm (Fig.   3b– c). [score:5]
b, c Pairwise comparisons based on cluster analyses revealed anther eight differentially expressed miRNAs between the first deciduous incisor (Di) and the second deciduous premolar (Dpm) (p < 0.01), and one (ssc-miR-127) between the deciduous canine (Dc) and Dpm (p < 0.05) during the three developmental stages. [score:4]
The present study indicated that these five miRNAs, including ssc-miR-103 and ssc-miR-107, ssc-miR-133a and ssc-miR-133b, and ssc-miR-127, may play key regulatory roles in different types of teeth during different stages and thus may play critical roles in tooth morphogenesis during early development in miniature pigs. [score:3]
In combination with our other results, this implies that ssc-miR-127, ssc-miR-103, and ssc-miR-107 may play a regulatory role in the morphogenesis of all kinds of teeth during different developmental stages. [score:3]
Expression levels of five miRNAs (ssc-miR-103, ssc-miR-107, ssc-miR-127, ssc-miR-133a, and ssc-miR-133b) were detected by real-time RT-PCR and microarray chip. [score:3]
Di, first deciduous incisor; Dc, deciduous canine; Dpm, second deciduous premolar; Dm, deciduous molar; E40, embryonic day 40; E50, embryonic day 50; E60, embryonic day 60 Ssc-mir-127 in situ expression reflected the microarray and real-time RT-PCR results (Fig.   6D1–F4). [score:3]
Di, first deciduous incisor; Dc, deciduous canine; Dpm, second deciduous premolar; Dm, deciduous molar; E40, embryonic day 40; E50, embryonic day 50; E60, embryonic day 60Ssc-mir-127 in situ expression reflected the microarray and real-time RT-PCR results (Fig.   6D1–F4). [score:3]
MiR-127 is an important regulator of MMP-13 in human chondrocytes and may contribute to the development of osteoarthritis [21]. [score:2]
For ssc-miR-127, deciduous molar were chose as the reference, the expression level is fairly higher in deciduous molar and submandibular gland compared to that in kidney and liver. [score:2]
Microarray, real-time RT-PCR, and in situ hybridization experiments revealed that ssc-miR-103 and ssc-miR-107, ssc-miR-133a and ssc-miR-133b, and ssc-miR-127 may play more important roles in Di and Dc, Dpm, and Dm, respectively, during different developmental stages. [score:2]
By clustering analysis, we predicted 11 unique miRNA sequences that belong to mir-103 and mir-107, mir-133a and mir-133b, and mir-127 isomiR families. [score:1]
The location of mir-127 was restricted in the inner enamel epithelium of the incisor, canine, and premolar (F1–F4). [score:1]
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6
[+] score: 75
The expression of pri-miR-433 and pri-miR-127 transcripts was observed to be strongly upregulated in the livers of SHP KO mice than in WT mice (Figure 4b). [score:6]
This is supported by the observation that both primary and mature miR-433 and miR-127 exhibit different fold induction in SHP KO mice, suggesting a differential and independent regulation of gene expression. [score:4]
The basal expression of pri-miR-127 appeared to be several fold higher than pri-miR-433, consistent with the higher expression level of miR-127 as compared to miR-433 [14]. [score:4]
The miRNA cluster containing miR-433 and miR-127 is located within the imprinted Dlk1/Gtl2 region that are only expressed from the maternal chromosome [21]. [score:3]
The expression of pri-miR-127 (∼1.2 kb) was verified by a Northern blot using probe C in SHP KO mice. [score:3]
MiR-127 and miR-136 are reported to be processed from a transcript (antiPeg11) that is antisense to Rtl1/Peg11, a paternally expressed intronless gene [22], [23]. [score:3]
Thus, we predict that the pri-miR-433 and pri-miR-127 would also be significantly increased but differentially expressed in SHP KO mice. [score:3]
The purple box shows the overlapping region of the miR-433 gene and miR-127 gene in a unidirectional manner. [score:2]
After bioinformatics analysis, we isolated the full-length primary transcripts of miR-433 and miR-127 and showed that they overlap in a 5′-3′ unidirectional way. [score:2]
Our recent study has identified the nuclear receptor small heterodimer partner (SHP) as a negative regulator of miR-433 and miR-127 gene transcription [14]. [score:2]
Both miR-433 and miR-127 exhibit increased expression in SHP KO mice as compared to the wild-type (WT) mice. [score:2]
Taken together, pri-miR-433 and pri-miR-127 were arranged in a tail-to-head orientation that were transcribed in the same direction, and shared a 297 bp overlapping region (the complete sequence for miR-433-127 gene cluster was deposited in GenBank, Accession number EU499599). [score:2]
Determining the detailed mechanisms how miR-433 and miR-127 are transcribed and regulated should provide insight into why such an unusual gene structure exists for these miRNAs. [score:2]
One interesting question is whether the two miRNAs arise from completely independent primary transcripts or whether the longer primary transcript is responsible for generating both miRNAs and a short one encodes miR-127. [score:1]
Non-conserved sequences were observed surrounding both of the TIS sites (G in bold green for pri-miR-433 and T in bold green for pri-miR-127) (Figure 4a). [score:1]
Chromosomal localization of miR-433 and miR-127 primary transcripts. [score:1]
A recent report assumed that the human miR-127 and miR-433 may be spliced from a large transcript including the whole cluster [20]. [score:1]
The length for the miR-433 and miR-127 gene is 1,842 bp and 1,124 bp, respectively. [score:1]
Northern blots were used to further verify the length and the overlapping pri-miR-433 and pri-miR-127 using total RNAs isolated from WT and SHP KO mice. [score:1]
After filtering the Blasting hits, we found that EST AK018276.1 (GenBank Accession number) includes miR-433 which is close to miR-127. [score:1]
Both the primary pri-miR-433 and pri-miR-127 were significantly enriched in SHP KO mice. [score:1]
Our study shows that the coupled miR-433 and miR-127 genes are transcribed from independent promoters by using overlapping genomic regions [14]. [score:1]
This study suggests an economical gene structure for miR-433 and miR-127, which may be a novel way of miRNA gene to maximize the genetics information in order to fit the complex physiological function of mammalian organism. [score:1]
Cloning of the human primary transcript encoding miR-433 and miR-127 will certainly determine if a similar overlapping gene structure exists in other mammalian species. [score:1]
We hypothesized that the miR-433 and miR-127 genes may use overlapping genomic regions, because the chromosomal location of miR-433 and miR-127 was only ∼1 kb apart (Table S1). [score:1]
The green and red letters and arrowheads point to the TIS and TTS of pri-miR-433 and pri-miR-127, respectively. [score:1]
The 3′-coding region of pri-miR-433 serves as the promoter region of pri-miR-127. [score:1]
Moreover, both the 1 [st] and 2 [nd] 3′RACE pri-miR-433 stopped at the predicted TTS but failed to amplify the full length pre-miR-127. [score:1]
Figure S1 Determining the transcriptional initiation site (TIS) by 5′-RACE and transcriptional termination site (TTS) by 3′-RACE for pri-miR-433 and pri-miR-127 gene. [score:1]
Interestingly, the fold increase of miR-433 (∼4 fold) and miR-127 (∼40 fold) in SHP KO mice appears to be drastically different. [score:1]
Pri-miR-433 stops at the 8 [th] nucleotide of miR-127 precursor (pre-miR-127). [score:1]
Finally, a contiguous transcript including both miR-433 and miR-127 could not be detected using miR-127 5′RACE, which stopped at the predicted pri-miR-127 TIS. [score:1]
0003574.g003 Figure 3 Full length sequences for pri-miR-433 and pri-miR-127 primary transcripts are presented. [score:1]
No sequences resembling a consensus TATA box (TATAAA) were identified near the TIS sites of pri-miR-433 and pri-miR-127, an observation that was similar to the human miR-34a gene [12]. [score:1]
Our study for the first time elucidates an overlapping gene structure for miR-433 and miR-127. [score:1]
The TIS of pri-miR-127 is located within the 3′-end of pri-miR-433 and the pri-miR-433 transcript contains the promoter region of the miR-127 gene. [score:1]
0003574.g004 Figure 4(a) Schematic of the miR-433 and miR-127 overlapping transcripts. [score:1]
Two transcripts were detected by probe B with predicted size of pri-miR-433 and pri-miR-127, respectively. [score:1]
0003574.g002 Figure 2 Chromosomal localization of miR-433 and miR-127 primary transcripts. [score:1]
Thus, we concluded that both RNAs represented the predicted pri-miR-433 and pri-miR-127. [score:1]
Probe B, whose sequence is complementary to the overlapping pri-miR-433 and pri-miR-127 coding sequence, hybridized to two RNA species corresponding to the size of pri-miR-433 and pri-miR-127, respectively. [score:1]
Determine transcriptional initiation and termination sites of pri-miR-433 and pri-miR-127 by RACE. [score:1]
Sequence analysis of AK018276.1 and its surrounding region in the chromosome showed that this EST stopped at the 6 [th] nucleotide of pre-miR-127. [score:1]
The 3′-terminal sequence of pri-miR-127 was also determined to be in complete agreement with the size predicted for the full length pri-miR-127 (1,124 bp). [score:1]
Probes A, B and C are designed with sequences complementary to the unique sequences of pri-miR-433, overlapping region of pri-miR-433 and pri-miR-127, and pri-miR-127, respectively. [score:1]
Table S1 Chromosomal location of the miR-433 and miR-127. [score:1]
In contrast to probe A, probe C (uniquely complementary to the 3′-terminal end of pre-miR-127) identified an RNA species with a size similar to that of pri-miR-127. [score:1]
Northern blot analysis of pri-miR-433 and pri-miR-127 primary transcript. [score:1]
Full length sequences for pri-miR-433 and pri-miR-127 primary transcripts are presented. [score:1]
Genes for miR-433 and miR-127 are located on chromosome 12 on the positive strand. [score:1]
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7
[+] score: 70
miR-21 was also reported to be up-regulated in squamous cell carcinoma [55] while miR-127, miR-322 and miR-146b are up-regulated during fetal lung development [56], [57]. [score:8]
Lastly, miR-127 was hypothesized to be involved in alveolar septation by inhibiting mRNA translation of specific targets [38]. [score:7]
Five miRNAs, miR-127, miR-21, miR-146b, miR-183, miR-184 were similarly up-regulated in c-Raf transgenic lung and human lung cancer therefore demonstrating clinical relevance of this particular disease mo del. [score:6]
The Affymetrix platform detected only the up-regulation of miR-127 in both female and male c-Raf transgenic mice (log [2] Ratio = 2.57 for females and 1.73 for males), and of miR-433 only in female c-Raf (log [2] Ratio = 2.10). [score:4]
Here miR-127 was highly up-regulated in male, but did not reach statistical significance (borderline at p<0.06; Table 1). [score:4]
Five miRNAs, miR-127, miR-21, miR-146b, miR-183, miR-184 were similarly up-regulated in c-Raf transgenic mouse lung and human lung cancer thus further validating this mo del as relevant for human lung cancer (Figure 7). [score:4]
Hence, much to our surprise, the two platforms correlated at best in identifying miR-127 as up-regulated in male, but not female, transgenic animals (Figure 1C). [score:4]
Differential miRNA expression was examined by quantitative real time PCR (qRT-PCR) of the eight regulated miRNAs (miR-21, miR-96, miR-127, miR-146b, miR-183, miR-184 and miR-322, miR-433). [score:4]
Shown is the expression of miR-21, miR-146b, miR-127, miR-433, miR-96, miR-183, miR-184 and miR-322 in WT and transgenic male and female mice. [score:3]
Specifically, with the Agilent platform a significant regulation of miR-21, miR-96, miR-127, miR-146b, miR-183, miR-184 and miR-322 was observed whereas for the Affymetrix platform significant regulation of miR-127 and miR-433 could only be evidenced. [score:3]
The qPCR results confirmed the significant over -expression of miR-127 and miR-433 in male and female c-Raf mice as identified by the. [score:3]
0078870.g005 Figure 5The 3′UTR sequence alignment of VLC, SLC10A3, MAPK4, GATA3, ANKRD27, IRS1, CRISPLD2 and ARL2 between Mus musculus and Homo sapiens species may possibly suggest conservation of seed sequences targeted by miR-21 (panel A), miR-146b (panel B), miR-127 (panel C), miR-433 (panel D), miR-96 (panel E), miR-183 (panel F), miR-184 (panel G) and miR-322 (panel H), respectively. [score:3]
miR-322, miR-127, and miR-433 are regulated similarly in organ and tumor development. [score:3]
0078870.g002 Figure 2 Shown is the expression of miR-21, miR-146b, miR-127, miR-433, miR-96, miR-183, miR-184 and miR-322 in WT and transgenic male and female mice. [score:3]
The 3′UTR sequence alignment of VLC, SLC10A3, MAPK4, GATA3, ANKRD27, IRS1, CRISPLD2 and ARL2 between Mus musculus and Homo sapiens species may possibly suggest conservation of seed sequences targeted by miR-21 (panel A), miR-146b (panel B), miR-127 (panel C), miR-433 (panel D), miR-96 (panel E), miR-183 (panel F), miR-184 (panel G) and miR-322 (panel H), respectively. [score:3]
Furthermore, miR-433 and miR-127 are within the same locus, and they are co-transcribed and co-regulated by estrogen-related receptors gamma [58]. [score:2]
The dendogram is suggestive for miR127 to be regulated in common when both platforms are compared while a third group of miRNAs is regulated in common amongst male transgenic mice as detected by the Agilent platform. [score:2]
Evidence has also been obtained to suggest a conserved gene structure and transcriptional regulation of miR-433 and miR-127 in mammals and that the miR-433/127 loci may have evolved from a common gene of origin. [score:2]
Prefabricated TaqMan MicroRNA Assays (containing microRNA-specific forward and reverse PCR primers and microRNA-specific Taqman MGB probe) were used to determine expression of miR-21 (ABI P/N 000397), miR-146b-5p (ABI P/N001097), miR-127 (ABI P/N000452), miR-433-3p (ABI P/N001028), miR-322 (ABI P/N001076), miR-184-3p (ABI P/N000485), miR-183 (ABI P/N002269), miR-96 (ABI P/N000186), miR-15a-5p (ABI P/N000389), miR-34a-5p (ABI P/N000426), miR-146a-5p (ABI P/N000468) and miR-182-5p (ABI P/N002599). [score:1]
Similarly, it is not clear why Affymetrix fails to see variations in all but two miRs (-127 and -433), since for example the probe for miR-184 has similar parameters to those for miR-127 and miR-433. [score:1]
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8
[+] score: 62
Sperm showed significantly higher (P<0.001) expression of imprinted and paternally expressed miRNAs (miR-296-3p, miR-296-5p, miR-483) and lower (P<0.001) expression of imprinted and maternally expressed miRNAs (miR-127, miR-127-5p) than those observed with somatic cells (Figure 1B). [score:9]
Using mouse as a mo del system, here we show that, similar to sperm, expression of imprinted and paternally expressed miRNAs (miR-296-3p, miR-296-5p, miR-483) were consistently higher (P<0.001), while those of imprinted and maternally expressed miRNA (miR-127, miR-127-5p) were consistently lower (P<0.001) in GS cells than in control embryonic stem (ES) cells. [score:7]
Similar to sperm, the expression of imprinted and paternally expressed miRNAs (miR-296-3p, miR-296-5p, miR-483) were consistently higher (P<0.001) while those of imprinted and maternally expressed miRNA (miR-127, miR-127-5p) were consistently lower (P<0.001) in GS cells than in control ES cells (Figure 2). [score:7]
It is likely that miR-127 may act by down -regulating its target proteins such as Bcl6 [48] and Brd2 [49] which are important for GS cell self-renewal and for the inhibition of differentiation, respectively [50], [51], [52], [53]. [score:6]
These imprinted gene clusters were specifically chosen because DNA methylation at both Dlk1-Dio3 IG-DMR and Igf2-H19 ICR is imprinted (i. e., DNA methylated) on paternal chromosome to suppress the expression of miR-127 and miR-483 from paternal and maternal chromosome, respectively. [score:5]
The Brd2 was also shown to be expressed at high levels in diplotene spermatocytes and round spermatids and at low levels in spermatogonia that negatively co-related with the expression pattern of miR-127 [49], [53]. [score:5]
Liu et al., [22] found that imprinted miRNAs encoded by Dlk1-Dio3 locus (e. g. miR-127 and miR-127-5p) had 717 putative targets that were related to multiple aspects of growth, differentiation, metabolism and other developmental processes in pluripotent cells. [score:4]
The miR-127 was preferentially expressed in immature mouse testes that principally contained mitotically active spermatogonia (day 7), meiosis I spermatocyte (day 12) and round spermatid (day 21), but remained at medium level in purified pachytene spermatocyte and round spermatid and declined in adult testis (containing fully differentiated germ cells and spermatozoa) [46]. [score:3]
Expressions of miR-296-3p, miR-296-5p, miR-127, miR-127-5p and miR-483 imprinted miRNAs in male germ-line (GS) and multipotent adult germ-line (maGS) stem cells. [score:3]
B: Expression of miR-296-3p, miR-296-5p, miR-127, miR-127-5p and miR-483 imprinted miRNAs in mouse somatic cells (open box), sperm (crossed box) and testis-tissue (closed box). [score:3]
Our result is similar to a previous study which showed high expression of miR-127 in testicular samples [46]. [score:3]
Expression of miR-296-3p (A), miR-296-5p (B), miR-127 (C), miR-127-5p (D) and miR-483 (E) imprinted miRNAs during in vitro differentiation of male germ-line (GS) and multipotent adult germ-line (maGS) stem cells. [score:3]
Three imprinted miRNAs, miR-127, miR-483 and miR-296, which are encoded from Dlk1-Dio3, Igf2-H19 and Gnas-Nespas imprinted gene clusters, respectively under the regulation of common ICRs (Dlk1-Dio3 IG-DMR, Igf2-H19 ICR and Gnas-Nespas DMR) for all miRNAs in the respective gene clusters were analyzed (Figure 1A) [20], [30], [31], [32]. [score:2]
It was also observed that, differentiating EBs generated from GS cells had significantly high level of miR-127 and miR-127-5p (Figure 4C and 4D), which might suggest their possible role during in vitro differentiation of SSC. [score:1]
All data were normalized to endogenous sno202 RNA as internal controls and calibrated on the STO cells, whose expression was considered one for all genes except for the miR-127 and miR-5p, for which sperm were used as a calibrator and considered one. [score:1]
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9
[+] score: 42
Before the onset of lupus, male and female NZB/W [F1] mice have comparable levels of lupus -associated miRNAsIn our previous study where we utilized only female NZB/W [F1] mice, we reported that a set of miRNAs including the miR-96-182-183 cluster, miR-155, miR-31, miR-127, and miR-379 were upregulated only in the splenocytes from diseased 36–40-wk-old (8–9 months) female NZB/W [F1] mice, but not in the splenocytes from the pre-diseased 16–18-wk-old (3–4 months) NZB/W [F1] mice when compared to those in the control NZW mice [34]. [score:7]
In our previous study where we utilized only female NZB/W [F1] mice, we reported that a set of miRNAs including the miR-96-182-183 cluster, miR-155, miR-31, miR-127, and miR-379 were upregulated only in the splenocytes from diseased 36–40-wk-old (8–9 months) female NZB/W [F1] mice, but not in the splenocytes from the pre-diseased 16–18-wk-old (3–4 months) NZB/W [F1] mice when compared to those in the control NZW mice [34]. [score:7]
We initially analyzed the expression of lupus -associated miRNAs including the miR-96-182-183 cluster, miR-155, miR-31, miR-127, miR-379, and miR-148a in splenocytes from male and female NZB/W [F1] mice at 17–18 wks old, an age before the onset of disease in NZB/W [F1] mice. [score:5]
Of the eight lupus -associated miRNAs analyzed in this study, only miR-127 and miR-379 displayed sexual differential expression before the onset of lupus in NZB/W [F1] (Figure  1). [score:3]
However, these two estrogen-lymphoma mice displayed large variations in expression of other miRNAs such as miR-127, miR-327, and miR-31 (Additional file 1: Figure S2). [score:3]
We recently reported that female NZB/W [F1] mice had increased expression of lupus -associated miRNAs such as the miR-182-96-183 cluster, miR-31, miR-155, miR-127, and miR-379 only at an age when lupus is manifested [34]. [score:3]
At 23 wks of age, the expression levels of miR-182, miR-183, miR-127, and miR-31 were significantly increased in female NZB/W [F1] mice when compared to age-matched male NZB/W [F1] mice (Figure  2A). [score:2]
There is also limited knowledge with regard to the immune regulatory function of miR-127 and miR-379. [score:2]
The sex differences in the expression of lupus -associated miRNAs, including the miR-182-96-183 cluster, miR-155, miR-31, miR-148a, miR-127, and miR-379, were markedly evident after the onset of lupus, especially at 30 wks of age when female NZB/W [F1] mice manifested moderate to severe lupus when compared to their male counterparts. [score:2]
Impressively, we found that after the onset of lupus, the expressions of lupus -associated miRNAs (miR-182-96-183, miR-31, miR-127, miR-379, and miR-148a, miR-155) were significantly increased in female NZB/W [F1] mice when compared to those in age-matched male mice. [score:2]
So far, there is limited knowledge about Dlk1-Gtl2 imprinted miRNA clusters such as miR-127 and miR-379 with regard to their function, especially their immune regulatory function. [score:2]
There was a trend (albeit not significant) of increase of miR-31 and miR-127 expressions in 32-wk-old estrogen -treated mice when compared to 32-wk-old placebo -treated control mice. [score:2]
Impressively, our previous microarray data indicated that in addition to miR-127 and miR-379, several other miRNAs from the Dlk1-Gtl2 region, including miR-433, miR-300, and miR-382, were also increased in MRL-lpr and B6-lpr mice [34]. [score:1]
miR-127 and miR-379 are encoded by a large miRNA cluster embedded in the mouse maternal imprinted region Dlk1-Gtl2 and human homologues DLK1-DIO3. [score:1]
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10
[+] score: 40
It is noteworthy that inhibition of miR-127 had only minor effect on IL-10 (Fig 6D) and that that inhibition of miR-411 had no obvious effect on the production of the above cytokines. [score:5]
However, for unknown reason, 5-aza-CdR treatment increased miR-154, miR-127, and miR-379 expression even in inactivated CD4 [+] T cells from MRL mice (medium, Fig 3B), and Con A activation did not further promote the effect of 5-aza-CdR on DLK1-Do3 miRNA expression in CD4 [+] T cells. [score:5]
We also showed that while antagomir-379 reduced miR-379 expression (S3D Fig) significantly, it has no effect on miR-127 expression (S3F Fig), suggesting the specificity of antagomirs. [score:5]
While did not induce any DLK1-Dio3 miRNA expression in unstimulated splenocytes (medium, Fig 3A), it did induce the expression of DLK1-Dio3 miRNAs including miR-154, miR-127, miR-379, miR-382, miR-433, and miR-300 substantially in Con A activated splenocytes (Con A, Fig 3A). [score:5]
We tested only miR-154, miR-127, miR-411, and miR-379 in cells from MRL- lpr mice since these four miRNAs were the most upregulated miRNAs in 5-aza-CdR treated splenocytes from MRL control mice. [score:4]
Impressively, of the 17 upregulated miRNAs in MRL- lpr mice, 11 miRNAs (miR-154, miR-127, miR-379, miR-382, miR-433, miR-300, miR-376b, miR-394, miR-299, miR-495, and miR-329) are located at a genomic imprinted DLK1-Dio3 region. [score:4]
In this study, we performed Taqman miRNA assays to confirm the upregulation of selected DLK1-Dio3 miRNAs such as miR-154, miR-127, miR-379, miR-382, miR-300, and miR-433 in MRL- lpr splenocytes. [score:3]
While miR-154 showed a similar increase in splenocytes and in different splenic immune cell subsets, the other six DLK1-Dio3 miRNAs including miR-127 (Fig 5B), miR-411 (Fig 5C), miR-379 (Fig 5D), miR-382 (Fig 5E), miR-433 (Fig 5F), and miR-300 (Fig 5G) were upregulated more dramatically in CD4 [-]CD19 [-] cells when compared to that in purified CD4 [+] T and CD19 [+] B cells. [score:3]
The expression levels of miR-154 (A), miR-127 (B), miR-411 (C), miR-379 (D), miR-382 (E), miR-433 (F), and miR-300 (G) in vehicle and 5-aza-CdR treated splenocytes, purified CD4 [+] T cells, CD19 [+] B cells, and splenic CD4 [-]CD19 [-] cells were quantified by Taqman miRNA assays. [score:2]
The dysregulation of DLK1-Dio3 miRNAs was also evident in B6- lpr and NZB/W [F1] lupus mice (such as miR-127 and miR-379) [28, 44], and in human lupus patients (such as miR-134, miR-379, and miR-433)[21, 29]. [score:2]
Unlike that we observed in splenocytes, there was a slight but significant increase of several DLK1-Dio3 miRNAs such as miR-154, miR-127, miR-379, and miR-382 even in the unstimulated CD4 [+] T cells from MRL mice (medium). [score:1]
There was a greater than 10 fold increase for selected DLK1-Dio3 miRNAs such as miR-154, miR-127, miR-411, miR-379 in 5-aza-CdR plus Con A treated MRL splenocytes. [score:1]
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[+] score: 31
miR-127 and miR-379, which were greatly upregulated in splenocytes from lpr mice, were moderately increased in diseased NZB/W mice. [score:6]
As shown in the figure 5, the expression levels of selected lupus -associated miRNAs including miR-96, miR-31, miR-127, miR-146a and miR-155 were significantly upregulated in freshly-isolated splenocytes from 3-4-month old MRL-lpr mice when compared to 1-month old MRL-lpr mice. [score:5]
However, the upregulation of miR-127 and miR-379 in 9-month old NZB/W is not significant when compared to 9-month old NZW mice (Fig. 4B). [score:3]
Overall, our data revealed that the expression changes in lupus -associated miRNAs such as miR-182-96-183, miR-31, miR-127, miR-379, miR-155, and miR-150 that were observed in splenocytes were also evident in purified splenic B and T cells. [score:3]
However, LPS activation did not induce miR-96, miR-31 and miR-127 expression changes in splenocytes. [score:3]
0014302.g005 Figure 5The expression levels of selected lupus -associated miRNAs (miR-96, miR-31, miR-127, miR-146a, and miR-155) in freshly-isolated (MRL-lpr-1 month), 24 hrs of LPS activated (MRL-lpr-1 month-LPS) splenocytes from 1-month old MRL-lpr mice, and freshly isolated splenocytes from 3-4 month old MRL-lpr mice (MRL-lpr-3-4 months) were analyzed by Real-time RT-PCR. [score:3]
The expression levels of selected lupus -associated miRNAs (miR-96, miR-31, miR-127, miR-146a, and miR-155) in freshly-isolated (MRL-lpr-1 month), 24 hrs of LPS activated (MRL-lpr-1 month-LPS) splenocytes from 1-month old MRL-lpr mice, and freshly isolated splenocytes from 3-4 month old MRL-lpr mice (MRL-lpr-3-4 months) were analyzed by Real-time RT-PCR. [score:3]
miR-127 and miR-379 were also significantly upregulated in 9-month old NZB/W mice when compared to 3-4-month old NZB/W. [score:3]
Consistent with the data observed in whole splenocytes, the expression of miR-182-96-183, miR-31, miR-127 and miR-379 was also significantly increased in purified splenic B cells and T cells from MRL-lpr mice when compared to MRL mice (Fig. 2B). [score:2]
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[+] score: 31
Literature mining revealed that the differentially expressed microRNAs miR-196a-5p, miR-127-3p and miR-206-3p are found to be expressed in hair follicles of mice skin [21]. [score:5]
We also determined the expression pattern of miRNAs such as miR-196a-5p, miR-127-3p, miR-411-5p, and miR-206-3p in UVR -induced SCC samples from wild type FVB mice. [score:3]
We found that a minimum of 12 to a maximum of 613 genes were targeted by miRNAs namely miR-127-3p and miR-322-5p respectively (Tables 1, 2, 3, 4). [score:3]
The expression patterns of miR-31-5p, miR-127-3p, miR-411-5p, miR-322-5p, miR-709, and miR-379-5p were similar to the microarray results in our profiling study among four mice groups namely WT, WT + UVR, TNFα KO, and TNFα KO+UVR following acute UVR treatment (Figure 2A). [score:3]
The B. is showing the expression pattern of miRNAs miR-31-5p, miR-196-5p, miR-127-3p, miR-206-3p, miR-411-5p, miR-709-5p, and miR-322-5p in UVR -induced SCC samples from wild type FVB mice. [score:3]
Some of the miRNAs were significantly down-regulated [miR-196a-5p (p=0.05), miR-709-5p (p=0.003), miR-206-3p (0.001), miR-411-5p (p=0.03)] along with others miR-127-3p, miR-322-5p in UVR -induced SCC samples (n=3) compared to the uninvolved skin (n=3) (Figure 2B). [score:3]
A. is showing the real time expression pattern of miR-31-5p, miR-127-3p, miR-411-5p, miR-322-5p, miR-709, and miR-379 in WT, WT + UVR, TNFα KO and TNFα KO + UVR mice. [score:3]
We also observed the differential expression of miR-196a-5p, miR-127-3p, and miR-206-3p in our samples. [score:3]
Figure 2 A. is showing the real time expression pattern of miR-31-5p, miR-127-3p, miR-411-5p, miR-322-5p, miR-709, and miR-379 in WT, WT + UVR, TNFα KO and TNFα KO + UVR mice. [score:3]
We also observed the suppression of miRNAs in SCC samples compared to uninvolved mice skin for miR-195-5p, miR-127-3p, miR-206-3p, miR-411-5p, miR-709-5p, and miR-322-5p. [score:2]
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[+] score: 25
Of a number of upregulated miRNAs, miRNA-376a, miR-127, miR-34a, miR-300, miR-342-3p were downregulated following metformin treatment in MCD-fed mice. [score:7]
Notably, miR-122, miR-194, miRNA-101b, and miRNA-705 were upregulated and miRNA-376a, miRNA-127, miRNA-34a, miRNA-300 and miRNA-342-3p were downregulated in the liver tissue of MCD-fed mice treated with or without metformin (Table IB and Fig. 6). [score:7]
The five downregulated miRNAs i. e., miRNA-376a, miRNA-127, miRNA-34a, miRNA-300 and miRNA-342-3p, were identical to five of the 71 upregulated miRNAs in control and MCD-fed mice. [score:7]
In addition, the downregulation of miR-127 facilitates hepatocyte regeneration after partial hepatectomy (17). [score:4]
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[+] score: 24
Analysis of global profiles of miRNA expression in skeletal muscle with microarray shows that expression of 4 miRNAs (miR-29a, miR-29b, miR-29c and miR-150) are up-regulated [23], whereas expression of 11 miRNAs (miR-379, miR-127, miR299-5p, miR-434-3p, miR-335, miR130a, miR-19b, miR-451, miR-148a, miR-199a and miR-152) are down-regulated in skeletal muscle of type 2 diabetic rats [23]. [score:13]
For example, it has been shown that expression of 4 miRNAs (miR-29a, miR-29b, miR-29c and miR-150) is up-regulated [23], whereas expression of 11 miRNAs (miR-379, miR-127, miR299-5p, miR-434-3p, miR-335, miR130a, miR-19b, miR-451, miR-148a, miR-199a and miR-152) is down-regulated in skeletal muscle of type 2 diabetic rats [23]. [score:11]
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[+] score: 23
In our hands, a significant up-regulation of H-2Kd was observed when comparing miR-29b with miR-127. [score:4]
In control mice, miR-127 or DOTAP treatment resulted in 53.5±4.8% or 58.5±6.2% target cell lysis, respectively. [score:3]
In the mDC CD11c [+]CD11b [+]B220 [−] population (Fig. 4A), miR-29b injection induced the up-regulation of CD40 and CD86 (B7-2) activation markers, as well as of the MHC class I molecule H-2Kd, compared to miR-127 and siRNA9.1 -injected mice (p<0.05). [score:3]
IL-6: P<0.05 for miR-29b vs miR-127 and miR-127 vs R848; IL-12: P<0.05 for miR-127 vs R848 (Kruskal-Wallis). [score:1]
Again, miR-29b, miR-7a and miR-376a stimulated IFNa production in sera of treated mice, in contrast to miR-127 and miR-210. [score:1]
RAW264.7 cells were plated four hours before stimulation with DOTAP-embedded miR-29b, 2′-O-Me -modified miR-29b, or the control miR-127 (750 nM working concentration). [score:1]
The immune-silent miR-127 served as negative control. [score:1]
9±32.0 nd 26.5±21.0 3.1±6.2 Cytokine content in serum from BALB/c mice was analysed by a BD Cytometric Bead Array two and seven hours following intravenous injection of miR29b, the immune-silent miR-127 or positive (R848) or negative (HBS) controls. [score:1]
For each marker, graphs represent the relative fluorescence intensity (RFI) of individual mice in two independent experiments (n = 3 mice for miR-29b and siRNA9.1, n = 4 mice for miR-127), and are representative of two other independent experiments. [score:1]
Briefly, 1 to 10×10 [5] activated HA–specific CD8 [+] T-cells from CL4-TCR mice were transferred to Ins-HA recipient mice previously injected with miR-29b, miR-127, or HBS negative control (Fig. 3A). [score:1]
are presented as the mean percentage of n = 5 mice for miR-29b, n = 3 for miR-127, and n = 4 mice in the HBS group from three independent experiments. [score:1]
Ins-HA mice were treated intravenously with miR-29b, miR-127, HBS buffer or DOTAP alone, eighteen hours before receiving HA-specific CTLs from CL4-TCR mice. [score:1]
BALB/c mice were injected intravenously with miR-29b, miR-127, or siRNA9.1. [score:1]
In contrast, a specific lysis of only 13.8±7.3% occurred in miR-29b mice (p<0.05 versus miR-127 and p<0.01 versus DOTAP). [score:1]
As shown in Fig. 1F and Table 1, miR-29b but not miR-127 greatly albeit transiently stimulated IL-6 and TNFa secretion in sera two hours after injection. [score:1]
Similarly, mice injected with miR-127 after transfer of 3×10 [5] or 5×10 [5] CD8 [+] T-cells all developed diabetes (data not shown). [score:1]
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[+] score: 22
Other miRNAs from this paper: mmu-mir-29b-1, mmu-mir-29a, mmu-mir-29c, mmu-mir-29b-2
Interestingly, when we overexpressed these miRNAs in fibroblasts, genetic enforcement of only miR-29c (Fig. 3d), but not miR-127-5p, abrogated the upregulation of VEGF expression induced by IGF2, implying that miR-29c may mediate the effect of IGF2 on VEGF. [score:8]
showed that transfection with the plasmids expressing miR-127-5p and miR-29c resulted in reduction of VEGF expression in fibroblasts (Fig. 3c). [score:5]
The BLOCK-iT [TM] Pol II miR RNAi Expression Vector Kit with EmGFP (Invitrogen) was used to create the vectors expressing miR-29c, miR-127-5p and the scrambled miRNA control (miR-CON). [score:5]
This approach allowed us to narrow the list of candidate miRNAs down to miR-127-5p and miR-29c, both of which satisfied the criteria of having seed regions that perfectly matched with the 3′UTR of VEGF (Fig. 3a) and were downregulated in fibroblasts upon IGF2 treatment (Fig. 3b). [score:4]
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[+] score: 22
In this study, there were 8 upregulated miRNAs (mir-193b-3p, mir-133a-1-3p, mir-133a-2-3p, mir-133a-1-5p, mir-133b-3p, mir-434-3p, mir-127-3p, mir-676-3p) and 1 downregulated miRNA (mir-215-5p) present as potential targets for differentiation between gram -negative and gram -positive bacterial infection. [score:9]
Following exposure to gram -positive bacteria in the injection and skin graft mo dels, 7 upregulated miRNAs (mir-193b-3p, mir-133a-1-3p, mir-133a-2-3p, mir-133b-3p, mir-434-3p, mir-127-3p, mir-676-3p) and 1 downregulated miRNA (mir-215-5p) were found. [score:7]
Upon gram -positive bacterial infection, 9 miRNAs (mir-193b-3p, mir-133a-1-3p, mir-133a-2-3p, mir-133a-1-5p, mir-133b-3p, mir-434-3p, mir-127-3p, mir-676-3p, mir-215-5p) showed upregulation greater than 4-fold with a p-value < 0.01. [score:4]
It was revealed that a total of 9 miRNAs (mir-193b-3p, mir-133a-1-3p, mir-133a-2-3p, mir-133a-1-5p, mir-133b-3p, mir-434-3p, mir-127-3p, mir-676-3p, mir-215-5p) showed differences greater than 4-fold with p-value < 0.01 between the 2 libraries (Table  1). [score:1]
Small RNA deep sequencing and qPCR results of five selected miRNAs (mir-133a-1-3p, mir-127-3p, mir-25-3p, mir-191-5p, and mir-215-5p) were generally in agreement, with a Pearson correlation value of 0.921 (Additional file 2). [score:1]
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[+] score: 22
We randomly picked 9 miRNAs (miR-337, miR-540-3p, miR-127, miR-434-5p, miR-329, miR-543-3p, miR-376a, miR-300, and miR-381) expressed from the Dlk1-Dio3 locus and validated their expression by qRT-PCR. [score:5]
The quantification results showed a significant increase in pri-miR-127 expression in myostatin knockout mice (Figure 4A). [score:4]
In fact, we showed that an increase in mature miR-127 expression is the result of activated transcription of the primary miR-127 transcript in myostatin knockout mice. [score:4]
To determine whether myostatin deficiency activates the transcription of chr12qF1 miRNAs, we further quantified the expression levels of the primary transcripts of miR-127 (pri-miR-127) and miR-411 (pri-miR-411) by qRT-PCR. [score:3]
108 ± 4.23, P = 0.091), whereas overexpression of the remaining 7 miRNAs (miR-127, miR-300, miR-329, miR-337-3p, miR-376a, miR-379, and miR-381) showed no significant effect on myotube diameter (Figure 2D). [score:3]
Figure 4(A) Quantitative RT-PCR analysis shows a significant increase in the expression of the primary transcript of miR-127 in myostatin -deficient skeletal muscle at 13 weeks of age. [score:3]
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[+] score: 19
For example, over expression of miR-127, a Dlk1-Dio3 mat NAFLD candidate, in pancreas islet cells suppresses insulin secretion and causes glucose intolerance [51]; additionally, miR-342 and miR-379 are upregulated in white adipose tissue of obese mice [52]. [score:8]
The other seven (miR-127, -136, -376c, -379, -409-3p, -411, and -495) were upregulated in both FLS W and FLS ob/ob mice relative to control mice; however, expression of these seven was higher in the FLS W mice than in FLS ob/ob mice. [score:6]
Furthermore, among these eight miRNAs, seven (miR-127, -136, -376c, -379, -409-3p, -411, and -495) were each upregulated in both FLS W and FLS ob/ob liver and mapped to the same maternally imprinted gene cluster delineated by the delta-like homolog 1 gene and the type III iodothyronine deiodinase gene (Dlk1-Dio3 mat) [30]. [score:4]
In the present study, we identified a novel set of NAFLD candidate miRNAs—miR-127, -136, -376c, -379, -409-3p, -411, and -495—that all mapped to the same miRNA cluster in the human Dlk1-Dio3 mat region. [score:1]
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[+] score: 19
This suggests that the miR-127 cluster may be involved in part of the regulation of the start of alveolar formation by inhibiting mRNA translation of specific targets without changes in mRNA levels. [score:8]
Within the miR-127 cluster, no miRNA targets were identified by miRNA/mRNA pairing (Figure 4C), while all had direct mRNA targets when miRNA/protein pairs were analyzed, such as miR-380-5p, miR-370, and miR-434. [score:6]
Interestingly, almost all 23 miRNAs in the miR-127 cluster that have the same strand orientation belong to miRNA Cluster 4 and have highest expression around E18. [score:3]
23 miRNAs belonging to the miR-127 cluster were increased, whereas all 6 miRNAs in the miRNA-17-92 cluster (mir-17, 18a, 19a, 19b-1, 20a, and 92-1) and 3 miRNAs (mir-20b, 90a-2 and 106a) in the miR-106a cluster that all belong to miRNA cluster 5 were dramatically decreased (Figure 4). [score:1]
The largest is the miR-127 cluster with greater than 50 members on mouse chromosome 12 (Chr. [score:1]
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[+] score: 17
Figure 3 A-E. is showing the expression pattern of miR-31-5p, miR-196-5p, miR-127-3p, miR-206-3p, and miR-411-5p in UVR -induced skin cSCC samples from SKH1 mice. [score:3]
A-E. is showing the expression pattern of miR-31-5p, miR-196-5p, miR-127-3p, miR-206-3p, and miR-411-5p in UVR -induced skin cSCC samples from SKH1 mice. [score:3]
These results support the consistent reproducible expression pattern of miR-31-5p, miR-196a-5p, miR-206-3p, miR-127-3p, and miR-411-5p in UVR -induced cSCC samples from SKH1 mice. [score:3]
However, other miRNAs, miR-196a-5p (p<0.0001); miR-206-3p (p<0.0001); miR-127-3p (p<0.0001); and miR-411-5p (p=0.0002) were significantly down-regulated in three to six UVR -induced cSCC samples from SKH1 mice compared to the uninvolved skin (Figure 3). [score:3]
To confirm the consistent pattern and involvement of UVR -induced selected miRNAs in cutaneous SCC samples, the expression of miR-31-5p, miR-196a-5p, miR-206-3p, miR-127-3p, and miR-411-5p were checked in cSCC samples collected from SKH1 mice induced by repeated UVR exposure. [score:3]
The suppression of miR-196a-5p, miR-206-3p, miR-127-3p, and miR-411-5p was observed in UVR -induced cSCC samples from SKH1 mice compared to uninvolved SCC free skin. [score:2]
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[+] score: 16
Other miRNAs from this paper: mmu-let-7g, mmu-let-7i, mmu-mir-23b, mmu-mir-27b, mmu-mir-126a, mmu-mir-145a, mmu-mir-181a-2, mmu-mir-182, mmu-mir-199a-1, mmu-mir-122, mmu-mir-143, mmu-mir-298, mmu-let-7d, 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-15a, mmu-mir-23a, mmu-mir-27a, mmu-mir-31, mmu-mir-98, mmu-mir-181a-1, mmu-mir-199a-2, mmu-mir-181b-1, mmu-mir-379, mmu-mir-181b-2, mmu-mir-449a, mmu-mir-451a, mmu-mir-466a, mmu-mir-486a, mmu-mir-671, mmu-mir-669a-1, mmu-mir-669b, mmu-mir-669a-2, mmu-mir-669a-3, mmu-mir-669c, mmu-mir-491, mmu-mir-700, mmu-mir-500, mmu-mir-18b, mmu-mir-466b-1, mmu-mir-466b-2, mmu-mir-466b-3, mmu-mir-466c-1, mmu-mir-466e, mmu-mir-466f-1, mmu-mir-466f-2, mmu-mir-466f-3, mmu-mir-466g, mmu-mir-466h, mmu-mir-466d, mmu-mir-466l, mmu-mir-669k, mmu-mir-669g, mmu-mir-669d, mmu-mir-466i, mmu-mir-669j, mmu-mir-669f, mmu-mir-669i, mmu-mir-669h, mmu-mir-466f-4, mmu-mir-466k, mmu-mir-466j, mmu-mir-669e, mmu-mir-669l, mmu-mir-669m-1, mmu-mir-669m-2, mmu-mir-669o, mmu-mir-669n, mmu-mir-466m, mmu-mir-669d-2, mmu-mir-466o, mmu-mir-669a-4, mmu-mir-669a-5, mmu-mir-466c-2, mmu-mir-669a-6, mmu-mir-466b-4, mmu-mir-669a-7, mmu-mir-466b-5, mmu-mir-669p-1, mmu-mir-669a-8, mmu-mir-466b-6, mmu-mir-669a-9, mmu-mir-466b-7, mmu-mir-669p-2, mmu-mir-669a-10, mmu-mir-669a-11, mmu-mir-669a-12, mmu-mir-466p, mmu-mir-466n, mmu-mir-486b, mmu-mir-466b-8, mmu-mir-466q, mmu-mir-145b, mmu-let-7j, mmu-mir-451b, mmu-let-7k, mmu-mir-126b, mmu-mir-466c-3
For example, miR-127 has been shown to participate in cancer development [85], miR-145 has been shown to control c-Myc expression through p53 [86], miR-199a regulates MET protooncogene and affects NF-KB expression [54], miR-379 affects brain neuronal development [87], [88], miR-451 affects erythroid differentiation [89], miR-126 affects angiogenic signaling and controls blood vessel development [90], miR-143 regulates ERK5 signaling and targets KRAS gene [91], miR-298 regulates CYPA3 expression [92] and miR-486 regulates kinase activity and tumor progression [93]. [score:16]
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[+] score: 15
Among the list, members of the miR-29 family, miR-203, miR-762, and miR-1224, showed upregulation, whereas members of the miR-107 family, miR-127 and miR-130a/b, miR-342-3p, miR-351, miR-379, miR-455, and miR-467a, were downregulated in both strains. [score:7]
miR-127 is part of the miRNA signature that is upregulated in acute myeloid leukaemia [45] and in nodal diffuse large B-cell lymphomas [46]. [score:4]
miRNAs that were differentially expressed only in the LW during aging include miR-29c, miR-705, miR-99a, miR-127, miR-130a, miR-145, miR-151-5p, miR-379, miR-467a, and miR-574-3p. [score:3]
These miRNAs include miR-107, miR-127, miR-130a/b, miR-145, miR-342, miR-351, miR-379, miR-455, and miR-467. [score:1]
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[+] score: 15
Other miRNAs from this paper: mmu-mir-1a-1, mmu-mir-134, mmu-mir-136, mmu-mir-154, mmu-mir-181a-2, mmu-mir-143, mmu-mir-196a-1, mmu-mir-196a-2, mmu-mir-21a, rno-mir-329, mmu-mir-329, mmu-mir-1a-2, mmu-mir-181a-1, mmu-mir-181b-1, mmu-mir-181c, mmu-mir-375, mmu-mir-379, mmu-mir-181b-2, rno-mir-21, rno-mir-127, rno-mir-134, rno-mir-136, rno-mir-143, rno-mir-154, rno-mir-181c, rno-mir-181a-2, rno-mir-181b-1, rno-mir-181b-2, rno-mir-196a, rno-mir-181a-1, mmu-mir-196b, rno-mir-196b-1, mmu-mir-412, mmu-mir-370, oar-mir-431, oar-mir-127, oar-mir-432, oar-mir-136, mmu-mir-431, mmu-mir-433, rno-mir-431, rno-mir-433, ssc-mir-181b-2, ssc-mir-181c, ssc-mir-136, ssc-mir-196a-2, ssc-mir-21, rno-mir-370, rno-mir-412, rno-mir-1, mmu-mir-485, mmu-mir-541, rno-mir-541, rno-mir-493, rno-mir-379, rno-mir-485, mmu-mir-668, bta-mir-21, bta-mir-181a-2, bta-mir-127, bta-mir-181b-2, bta-mir-181c, mmu-mir-181d, mmu-mir-493, rno-mir-181d, rno-mir-196c, rno-mir-375, mmu-mir-1b, bta-mir-1-2, bta-mir-1-1, bta-mir-134, bta-mir-136, bta-mir-143, bta-mir-154a, bta-mir-181d, bta-mir-196a-2, bta-mir-196a-1, bta-mir-196b, bta-mir-329a, bta-mir-329b, bta-mir-370, bta-mir-375, bta-mir-379, bta-mir-412, bta-mir-431, bta-mir-432, bta-mir-433, bta-mir-485, bta-mir-493, bta-mir-541, bta-mir-181a-1, bta-mir-181b-1, ssc-mir-1, ssc-mir-181a-1, mmu-mir-432, rno-mir-668, ssc-mir-143, ssc-mir-181a-2, ssc-mir-181b-1, ssc-mir-181d, ssc-mir-196b-1, ssc-mir-127, ssc-mir-432, oar-mir-21, oar-mir-181a-1, oar-mir-493, oar-mir-433, oar-mir-370, oar-mir-379, oar-mir-329b, oar-mir-329a, oar-mir-134, oar-mir-668, oar-mir-485, oar-mir-154a, oar-mir-154b, oar-mir-541, oar-mir-412, mmu-mir-21b, mmu-mir-21c, ssc-mir-196a-1, ssc-mir-196b-2, ssc-mir-370, ssc-mir-493, bta-mir-154c, bta-mir-154b, oar-mir-143, oar-mir-181a-2, chi-mir-1, chi-mir-127, chi-mir-134, chi-mir-136, chi-mir-143, chi-mir-154a, chi-mir-154b, chi-mir-181b, chi-mir-181c, chi-mir-181d, chi-mir-196a, chi-mir-196b, chi-mir-21, chi-mir-329a, chi-mir-329b, chi-mir-379, chi-mir-412, chi-mir-432, chi-mir-433, chi-mir-485, chi-mir-493, rno-mir-196b-2, bta-mir-668, ssc-mir-375
The miR-127 family has been reported to play a role in regulating the expression of the tumor suppressor gene BCL6, in cell proliferation, and in apoptosis [32]. [score:6]
Most reads (highest expression) were from the miR-379 family; next was miR-127 family with 5,235 reads. [score:3]
By comparing with sheep miRNA sequences, we found that 5 miRNA families containing miR-127, miR-136, miR-154, miR-229 and miR-379, were conserved in all these species It is, therefore, tempting to speculated that these 5 miRNA families are critical in mammal development. [score:2]
Another study found that the miR-127 family plays an important role in fetal lung development [33]. [score:2]
We suggest that miR-127 may play a part in skin follicle cell apoptosis and proliferation. [score:1]
Most of the miRNAs were sequenced only a few times, whereas miR-127, miR-154 and miR-375 were sequenced thousands of times. [score:1]
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[+] score: 15
Unlike miR-434 and miR-136 (PAM class C), miR-127 expression gradually decreases during the differentiation process (PAM class A), a pattern inversely correlated to that of Rtl1 expression in ES cells, as assayed by Quantitative Reverse-transcriptase PCR (Q-RT-PCR; Figure 2D). [score:4]
Among these, a short cluster of maternally expressed miRNAs genes (miR-431, miR-433, miR-127, miR-434 and miR-136) is transcribed and processed from an antisense gene to the paternally expressed Retrotransposon-like 1 (Rtl1) gene, the recently characterized protein product of which appears to be indispensable for mouse foetal development [37]. [score:4]
The three miRNAs can be further distinguished based on their expression profiles and respective cloning frequencies, with miR-127 contributing alone 10% of all cloned miRNAs at D0. [score:3]
This unravels a major contribution of miR-127. [score:1]
Notably, the miR-290_295 cluster, miR-127 and miR-22 contribute collectively to more than 65% of all cellular miRNAs of undifferentiated ES cells, and their respective abundance consistently decreases during early differentiation. [score:1]
Our time-course analysis revealed that of these five miRNAs, only miR-127, miR-434 and miR-136, are likely to contribute to Rtl1 silencing in ES cells (Figure 2D) because their cloning frequencies largely exceeds that of the other members of the cluster, which accumulate at background level (Figure 2C, Dataset S1). [score:1]
We conclude that miR-127 is likely the major contributor of Rtl1 silencing in differentiating mouse ES cells. [score:1]
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[+] score: 14
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-20a, hsa-mir-21, hsa-mir-22, hsa-mir-26a-1, hsa-mir-99a, hsa-mir-103a-2, hsa-mir-103a-1, hsa-mir-106a, hsa-mir-107, mmu-let-7g, mmu-let-7i, mmu-mir-99a, mmu-mir-101a, mmu-mir-125a, mmu-mir-125b-2, mmu-mir-126a, mmu-mir-145a, mmu-mir-146a, mmu-mir-129-1, mmu-mir-206, hsa-mir-129-1, hsa-mir-148a, mmu-mir-122, mmu-mir-143, hsa-mir-139, hsa-mir-221, hsa-mir-222, hsa-mir-223, mmu-let-7d, mmu-mir-106a, hsa-let-7g, hsa-let-7i, hsa-mir-122, hsa-mir-125b-1, hsa-mir-143, hsa-mir-145, hsa-mir-125a, hsa-mir-125b-2, hsa-mir-126, hsa-mir-127, hsa-mir-129-2, hsa-mir-146a, hsa-mir-206, mmu-mir-148a, 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-20a, mmu-mir-21a, mmu-mir-22, mmu-mir-26a-1, mmu-mir-129-2, mmu-mir-103-1, mmu-mir-103-2, rno-let-7d, rno-mir-335, rno-mir-129-2, rno-mir-20a, mmu-mir-107, mmu-mir-17, mmu-mir-139, mmu-mir-223, mmu-mir-26a-2, mmu-mir-221, mmu-mir-222, mmu-mir-125b-1, hsa-mir-26a-2, hsa-mir-335, mmu-mir-335, 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-17-1, rno-mir-18a, rno-mir-21, rno-mir-22, rno-mir-26a, rno-mir-99a, rno-mir-101a, rno-mir-103-2, rno-mir-103-1, rno-mir-107, rno-mir-122, rno-mir-125a, rno-mir-125b-1, rno-mir-125b-2, rno-mir-126a, rno-mir-127, rno-mir-129-1, rno-mir-139, rno-mir-143, rno-mir-145, rno-mir-146a, rno-mir-206, rno-mir-221, rno-mir-222, rno-mir-223, hsa-mir-196b, mmu-mir-196b, rno-mir-196b-1, hsa-mir-20b, hsa-mir-451a, mmu-mir-451a, rno-mir-451, hsa-mir-486-1, hsa-mir-499a, mmu-mir-486a, mmu-mir-20b, rno-mir-20b, rno-mir-499, mmu-mir-499, mmu-mir-708, hsa-mir-708, rno-mir-17-2, rno-mir-708, hsa-mir-103b-1, hsa-mir-103b-2, mmu-mir-486b, rno-mir-126b, hsa-mir-451b, hsa-mir-499b, mmu-mir-145b, mmu-mir-21b, mmu-let-7j, mmu-mir-130c, mmu-mir-21c, mmu-mir-451b, mmu-let-7k, hsa-mir-486-2, mmu-mir-129b, mmu-mir-126b, rno-let-7g, rno-mir-148a, rno-mir-196b-2, rno-mir-486
After 6 and 12 wks of E [2] exposure, 15 miRNAs were down-regulated, e. g., miR-22, miR-99a, miR-106a, miR-127, miR-499, and 19 miRNAs were-up-regulated, e. g., miR-17-5p, miR-20a, miR-21, miR-129-3p, miR-106a, miR-22, and miR-127. [score:7]
Genes targeted by three of the altered miRNAs were examined: miR-20a regulates E2F1, miR-106a regulates RBI, and miR-127 regulates BCL6. [score:6]
Western blot of mammary gland lysates after 12 wks of E [2] showed that levels of RBI and E2F1 were decreased and BCL6 protein was increased, data that are in agreement with the increase miR-20a and miR-106a and the decrease in miR-127 detected [198]. [score:1]
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[+] score: 14
Imprinted gene expression profiles in the Dlk1-Dio3 region were determined, including those of paternally expressed genes, Dlk1, Rtl1 and Dio3, and maternally expressed genes, Meg3, Meg8 and antisense Rtl1 (encoding miR433 and miR127). [score:7]
PCR was carried out using primers for the paternally expressed genes, Dlk1, Rtl1, and Dio3, and the maternally expressed genes, Meg3, Meg8, and antisense Rtl1 encoding miR433 and miR127. [score:4]
In the Dlk1-Dio3 region, the maternally expressed genes can produce non-coding RNAs, including mir-431, mir-433, mir-127, mir-432 and mir-136. [score:3]
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[+] score: 13
Members of the miR-99 family (miR99a, and miR100, the fourth and seventh most abundant mouse sRNAs) are miRNAs that have been shown to co-enrich with polyribosomes in mammalian neurons, and regulate the mammalian target of rapamycin (mTOR) pathway 46. miR22, the eighth most abundant mouse sRNA, is important for cerebellar development, and in adults has been shown to protect neurons from neurodegeneration, and is down regulated in both Huntington’s and Alzheimer’s disease 47. miR127, along with a cluster of miRNAs found on chromosome14q32, is maternally expressed, and the down regulation of miRNAs within this cluster (including miR127) has been linked to schizophrenia 48. [score:11]
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]
The third, fourth, seventh, eighth and ninth mapped to neuronal associated microRNAs, including miR128, miR99, miR100, miR22, and miR127 (21–22 nt). [score:1]
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[+] score: 10
The array uncovered the induction of 117 miRNAs with the signal intensity ≥500 (the fluorescence amount of each miRNA probe is measured by a photo multiplier tube or charge-coupled device and signal scaled across the range of detection for the platform) in GA muscle (Table 1, Fig. 1A and 1B), including the highly downregulated miRNAs (≥1.5-fold) miR-194-5p, miR-101b-3p, miR-148a-3p, miR-199b-5p, miR-335-5p, miR-127-3p, miR-379-5p, miR-541-5p, miR-382-5p, miR-329-3p, miR-299-5p and miR-434-3p, and the highly up-regulated miRNAs (≥1.5 fold), miR-146b-5p and miR-146a-5p (Fig. 1C). [score:5]
The differentially expressed miRNAs in earlier studies appeared consistently in mouse skeletal muscle from our study; for example, the expression pattern of miR-146a-5p, miR-146b-5p, miR-434-3p, miR-127-3p, and miR-148a-3p are similar to previous studies. [score:5]
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[+] score: 10
In the results of the splenocytes from the MRL/lpr mice, ASC treatment did not change the miR expression significantly, but cyclophosphamide treatment decreased the expression of miR-31-5p, miR-96-5p, miR-127-3p, miR-182-5p, miR-183-5p, and miR-379-5p significantly compared with the saline-treatment. [score:4]
In splenocytes from the MRL-lpr mice (the samples in our previous study), the expression levels of miR-18a-5p, miR-31-5p, miR-96-5p, miR-127-3p, miR-182-5p, miR-183-5p, and miR-379-5p were significantly higher, while those of miR-101a-3p and miR150-5p were significantly lower in the C group than in the N group. [score:3]
The expression levels of miR-31-5p, miR-96-5p, miR-127-3p, miR-182-5p, miR-183-5p, and miR-379-5p 5p in the Y group were significantly lower than in the C group (Supplementary Fig. 3). [score:3]
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[+] score: 9
To determine the regulation of SHP in miRNAs expression and function, we recently cloned two overlapping primary transcripts encoding miR-433 and miR-127, respectively [11]. [score:4]
Interestingly, the basal expression of miR-206 was about 2-fold higher than miR-133b, suggesting that the paired miR-206 and miR-133b might be derived from two primary transcripts under the control of independent promoters, similar to the paired miR-433 and miR-127 [11], [12]. [score:3]
Our previous studies identified (CT)n or (CTT)n simple sequence repeats in the promoter of the primary transcript of miR-127 [11], [12]. [score:1]
The coupled miR-433 and miR-127 were transcribed from independent promoters repressed by SHP in a compact space by using overlapping genomic regions [12]. [score:1]
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[+] score: 9
For example, the expression of miR-127 was up-regulated to a greater extent in epigenetically unmasked cancer cells. [score:6]
The DNA methylation level and histone modification (histone acetylation and histone methylation) status at the identified promoter regions of miR-127 presented significant correlations with the expression of mature miR-127 32. [score:3]
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[+] score: 9
For example, miR-127, which is down-regulated in prostate, colon and bladder tumors relative to matched normal tissues, is up-regulated in cell lines derived from these tumor types following inhibition of DNA demethylation and histone deacetylase [40]. [score:9]
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[+] score: 8
The results given in Table S1 show that expressions of miR-100, miR-125b, miR-135a, miR-138, miR-150, miR-146a, miR-221 which were decreased in HD cell mo del [33] were also decreased in and the expressions of miR-127-3p and miR-214 were increased in both STHdh [Q111]/Hdh [Q111] cells [33] and the R6/2 mouse mo del. [score:5]
, miR-127 and miR-214) were increased and expressions of three miRNAs (viz. [score:3]
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[+] score: 7
At 6 h, 40 miRNAs were upregulated (such as miR-146b-5p, miR-27b-3p and let-7f-5p) and 20 were downregulated (such as miR-127-5p, miR-3094-3p and miR-30c-1-3p) (Figure 3B; Table 1). [score:7]
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[+] score: 7
For example, up-regulation of miR-127/125b/154/323/368/370/381 is associated with leukemia cells with t(15;17), and up-regulation of miR-126* is associated with those with t(8;21). [score:7]
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[+] score: 7
The analysis of randomly-chosen miRNAs from clusters 1 and 2 (miR-654-3p, mir-369-3p, miR-495, miR-370-5p, miR-127-5p and miR-376c-3p) in tumor cell lines confirmed their downregulation (Figure 1d). [score:4]
Cahill and colleagues have shown that human derived BRAFT1799A- and RET/PTC-bearing thyroid tumor cells, KAT10 and TPC-1 respectively, express lower levels of 14q32-encoded miRNAs miR-323-3p, miR-370-5p, miR-127-3p, miR-299 and miR-154 [22, 23]. [score:3]
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[+] score: 7
Similarly, Ying et al. (49) reported that downregulation of miR-127 could impair the infiltration and function of Mφ, which was contributed to the decreased pathology of ALI. [score:4]
For example, Li et al. (9) reported that cardiopulmonary bypass -induced ALI could lead to dynamic changes in miRNA expression in lungs, including miR-21, miR-127, miR-145, and miR-204. [score:3]
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[+] score: 7
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-15a, hsa-mir-16-1, hsa-mir-17, hsa-mir-18a, hsa-mir-21, hsa-mir-24-1, hsa-mir-24-2, hsa-mir-25, hsa-mir-27a, hsa-mir-30a, hsa-mir-31, hsa-mir-29b-1, hsa-mir-29b-2, hsa-mir-103a-2, hsa-mir-103a-1, hsa-mir-16-2, mmu-let-7g, mmu-let-7i, mmu-mir-15b, mmu-mir-29b-1, mmu-mir-30a, mmu-mir-30b, mmu-mir-125a, mmu-mir-125b-2, mmu-mir-126a, mmu-mir-9-2, mmu-mir-141, mmu-mir-145a, mmu-mir-155, mmu-mir-10b, mmu-mir-24-1, mmu-mir-205, mmu-mir-206, hsa-mir-30c-2, hsa-mir-30d, mmu-mir-30e, hsa-mir-10b, hsa-mir-34a, hsa-mir-205, hsa-mir-221, mmu-mir-290a, mmu-mir-34c, mmu-mir-34b, mmu-let-7d, mmu-mir-106b, hsa-let-7g, hsa-let-7i, hsa-mir-15b, hsa-mir-30b, hsa-mir-125b-1, hsa-mir-141, hsa-mir-145, hsa-mir-9-1, hsa-mir-9-2, hsa-mir-9-3, hsa-mir-125a, hsa-mir-125b-2, hsa-mir-126, hsa-mir-127, hsa-mir-206, mmu-mir-30c-1, mmu-mir-30c-2, mmu-mir-30d, 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-15a, mmu-mir-16-1, mmu-mir-16-2, mmu-mir-18a, mmu-mir-21a, mmu-mir-24-2, mmu-mir-27a, mmu-mir-31, mmu-mir-34a, mmu-mir-103-1, mmu-mir-103-2, mmu-mir-322, hsa-mir-200c, hsa-mir-155, mmu-mir-17, mmu-mir-25, mmu-mir-200c, mmu-mir-221, mmu-mir-29b-2, mmu-mir-9-1, mmu-mir-9-3, mmu-mir-125b-1, hsa-mir-106b, hsa-mir-30c-1, hsa-mir-34b, hsa-mir-34c, hsa-mir-30e, hsa-mir-373, hsa-mir-20b, hsa-mir-520c, hsa-mir-503, mmu-mir-20b, mmu-mir-503, hsa-mir-103b-1, hsa-mir-103b-2, mmu-mir-145b, mmu-mir-21b, mmu-let-7j, mmu-mir-21c, mmu-mir-30f, mmu-let-7k, mmu-mir-126b, mmu-mir-290b, mmu-mir-9b-2, mmu-mir-9b-1, mmu-mir-9b-3
For example, miR-127, which is downregulated in human cancer cells, has been reported to be located within a CpG island and highly up-regulated by DNA demethylation and histone acetylation [109]. [score:7]
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[+] score: 6
In this study, five miRNAs (miR-29a, miR-29b, miR-126*, miR-127-3p, miR324-3p) were found upregulated and four (miR-188-5p, miR-25, miR-320a, miR-346) downregulated in both quiescent and active UC compared to healthy controls (Fasseu et al., 2010). [score:6]
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[+] score: 6
Knockdown of lncRNA MEG3 inhibits viability, migration, and invasion and promotes apoptosis by sponging miR-127 in osteosarcoma cell. [score:4]
MEG3 has been described to be a ceRNA that regulates miR-223 (Zhang Y. et al., 2017), miR-183 (Zhang and Feng, 2017), miR-421 (Zhang W. et al., 2017), and miR-127 (Wang and Kong, 2018). [score:2]
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[+] score: 6
Also, miR-127 was shown to regulate Bcl6 [53]. [score:2]
Three microRNAs in this region, miR-431, miR-127, and miR-136, were shown previously to regulate Peg11 through a siRNA-like mechanism [52]. [score:2]
This conclusion is based on the observation that our cDNA begins at the end of miR-431 precursor and ends at the beginning of miR-127 precursor. [score:1]
org/microrna/) Meg3mmu-miR-770 # Bmp1, Bmp15, Capn3, Casq2, Fosb, Lmna, Mb, Obscn, Peg10, Ppp1ca, Sspn, Tmod1, Trp53 Unidentified mmu-miR-673 Camk2a, Camk2b, Camk2d, Camk2g, Dnmt1, Mtpn, Myh6, Ndn, Pax3, Rbl1, Sln, Tnnt1, Wnt1 Unidentifiedmmu-miR-493 # Cacng5, Camk2g, Cdkn1c, Ctcf, Dag1, Fhl1, Fos, Hras1, Jun, Mib2, Mtap, Peg10, Shh, Tmod1 Unidentifiedmmu-miR-337 # Capza2, Des, Dmd, Dnmt3a, Myh8, Mypn, Nfatc1, Plagl2, Pvalb, Sgcb, Snta1, Tpm3, Trp53 Unidentified mmu-miR-540 Akt3, Bmp2, Bmp7, Capzb, Emd, Itga7, Itgb1, Msc, Myog, Nkx2-5, Pten, Rhoa, Sln, Tlx1, Vim Unidentifiedmmu-miR-665 # Casq2, Igf2, Junb, Ldb3, Peg10, Magel2, Nnat, Pax3, Ryr1, Sntb2, Tln1, Tpm2, Trp53, TtnAnti-Peg11 $ mmu-miR-431 # d Camk2b, Casq1, Dtna, E2f1, Fgf4, Gata3, Igf1, Kit, Max, Peg10, Plagl2, Ppp3r1, Sgcd, Tcf21Anti-Peg11 $ mmu-miR-433 # Bmpr1b, Capza1, Creb1, Ctcf, E2f3, Gata6, Isl1, Jak2, Myh9, Peg10, Plagl2, Ppp3r1, Sntg1Anti-Peg11 $ mmu-miR-127 # d e Auts2, Bcl6, Camk2d, Cdc42, Creb5, E2f3, Igf2, Myo1c, Otx1, Plagl2, Pitx2. [score:1]
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[+] score: 5
For example, miR-7 regulates the expression of A53T α-synuclein [51], miR-7 and -153 participate in SNCA transcription [23, 51], the function of miR-1224, -184 and let-7i-3p/5p is regulated by leucine-rich repeat kinase 2 (LRRK2) [52, 53], and miR-127-5p and -16-5p play their roles in glucocerebrosidase (GBA) pathway [54]. [score:5]
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[+] score: 5
Indeed, mmu-miR-127 and mmu-miR-337 (encoded within the anti- Rtl1 transcript), both displayed decreased expression conservatively estimated at >1000-fold, while mmu-miR-134 and mmu-miR-494 (encoded within the Mirg cluster) showed >1000-fold and >100-fold decreased expression, respectively. [score:5]
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[+] score: 5
Support for the susceptibility of these miRNAs to epigenetic regulation can be found in a study that demonstrated chromatin modifying drugs could activate mir-127 expression in multiple human cancer cell lines [58]. [score:4]
Individual TSSs for mir-433 and mir-127 have also been identified in an independent study [57]. [score:1]
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[+] score: 4
For example, miR-204 is primarily expressed in insulinomas and co-localizes mainly with insulin [43]; miR-127-3p and miR-184 are positively correlated with insulin biosynthesis and negatively correlated with glucose-stimulated insulin secretion (GSIS) [44]; miR-148 controls the insulin content in β-cells through regulation of the insulin repressor SOX6 [45] and miR-29 contributes to pancreatic β-cell dysfunction in prediabetic NOD Mice [46], and affects the release of insulin from β-cells by silencing of monocarboxylate transporter (MCT1) [47]. [score:4]
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[+] score: 4
Tryndyak V. P. Ross S. A. Beland F. A. Pogribny I. P. Down-regulation of the microRNAs miR-34a, miR-127, and miR-200b in rat liver during hepatocarcinogenesis induced by a methyl -deficient dietMol. [score:4]
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[+] score: 4
Other miRNAs from this paper: hsa-mir-127
Jiang H MicroRNA-127-3p promotes glioblastoma cell migration and invasion by targeting the tumor-suppressor gene SEPT7Oncol. [score:4]
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[+] score: 4
In the order of the significance score by SAM, 15 up-regulated miRNAs are mmu-miR-127, mmu-miR-410, mmu-miR-433, mmu-miR-138, mmu-miR-181c, mmu-miR-382, mmu-miR-19b, mmu-miR-381, mmu-miR-666-3p, mmu-miR-376a, mmu-miR-873, mmu-miR-181a, mmu-miR-383, mmu-miR-181b, and mmu-miR-99b. [score:4]
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[+] score: 4
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-22, hsa-mir-29a, hsa-mir-30a, hsa-mir-29b-1, hsa-mir-29b-2, mmu-let-7g, mmu-let-7i, mmu-mir-1a-1, mmu-mir-29b-1, mmu-mir-30a, mmu-mir-132, mmu-mir-133a-1, mmu-mir-136, mmu-mir-144, mmu-mir-146a, mmu-mir-152, mmu-mir-155, mmu-mir-10b, mmu-mir-185, mmu-mir-190a, mmu-mir-193a, mmu-mir-203, mmu-mir-206, hsa-mir-148a, mmu-mir-143, hsa-mir-10b, hsa-mir-34a, hsa-mir-203a, hsa-mir-215, mmu-mir-34c, mmu-mir-34b, mmu-let-7d, hsa-let-7g, hsa-let-7i, hsa-mir-1-2, hsa-mir-132, hsa-mir-133a-1, hsa-mir-133a-2, hsa-mir-143, hsa-mir-144, hsa-mir-152, hsa-mir-127, hsa-mir-136, hsa-mir-146a, hsa-mir-185, hsa-mir-190a, hsa-mir-193a, hsa-mir-206, mmu-mir-148a, 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-22, mmu-mir-29a, mmu-mir-29c, mmu-mir-34a, mmu-mir-337, hsa-mir-1-1, mmu-mir-1a-2, hsa-mir-155, mmu-mir-29b-2, hsa-mir-29c, hsa-mir-34b, hsa-mir-34c, hsa-mir-378a, mmu-mir-378a, hsa-mir-337, mmu-mir-133a-2, mmu-mir-133b, hsa-mir-133b, mmu-mir-215, mmu-mir-411, mmu-mir-434, hsa-mir-486-1, hsa-mir-146b, hsa-mir-193b, mmu-mir-486a, mmu-mir-540, hsa-mir-92b, hsa-mir-411, hsa-mir-378d-2, mmu-mir-146b, mmu-mir-193b, mmu-mir-92b, mmu-mir-872, mmu-mir-1b, mmu-mir-3071, mmu-mir-486b, hsa-mir-378b, hsa-mir-378c, hsa-mir-378d-1, hsa-mir-378e, hsa-mir-378f, hsa-mir-378g, hsa-mir-378h, hsa-mir-378i, mmu-mir-378b, hsa-mir-203b, mmu-mir-3544, hsa-mir-378j, mmu-mir-133c, mmu-let-7j, mmu-mir-378c, mmu-mir-378d, mmu-let-7k, hsa-mir-486-2
MiR-127 was identified as a cardiac valve-enriched miRNA [34]; however, there were no previous reports on its role in skeletal muscle development. [score:2]
miRNA Fold Change P-value mmu-miR-337-5p −5.2 0.0149 mmu-miR-3544-3p −5.1 0.0147 mmu-miR-540-5p −4.9 0.0200mmu-miR-337-3p [a] −3.0 0.0324mmu-miR-3544-5p [a] −3.0 0.0308 mmu-miR-434-3p −2.1 0.0001 mmu-miR-3071-5p −2.0 0.0004mmu-miR-136-3p [a] −2.0 0.0004mmu-miR-3071-3p [a] −1.6 0.0000 mmu-miR-136-5p −1.6 0.0000 mmu-miR-143-5p −1.2 0.0004 mmu-miR-190a-5p −1.0 0.0139 mmu-miR-872-3p −0.9 0.0152 mmu-miR-193a-3p −0.9 0.0164 mmu-miR-144-3p −0.8 0.0298 mmu-miR-127-3p −0.7 0. 0002mmu-miR-434-5p [a] −0.6 0.0082 mmu-miR-148a-3p −0.6 0.0130 mmu-miR-411-5p −0.6 0.0091 a miRNA* (passenger) strand processed from opposite arm of the mature miRNA. [score:1]
Of the eight miRNAs located in the imprinted Dlk1-Dio3 region, four miRNAs, miR-127, -136, -434, and -3071, are located within anti-Rtl1, which contains seven miRNAs (Fig. S3, based on miRbase). [score:1]
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[+] score: 4
Other miRNAs from this paper: hsa-mir-127, hsa-mir-494, mmu-mir-494
Eight out of the ten analyzed 14q32 miRNAs were expressed by A549 cells at baseline conditions (namely miR-127,-379, -382, -409-3p, -412, -431, -494-3p and -543; Supplementary Figure 3B). [score:3]
We therefore analyzed a subset (n = 10) of those miRNAs (miR-127, -300, 370, -379, -382, -409-3p, -412, -431, -494-3p and -543) in a series of 57 NSCLC patients. [score:1]
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[+] score: 3
Our studies also showed that miR-127 and miR-409-3p were strongly expressed at all stages of human embryonic chondrocyte differentiation. [score:3]
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53
[+] score: 3
Other miRNAs from this paper: mmu-mir-136
Two miRNA genes, miR-127 and miR-136, have been shown to be part of an imprinted domain responsible for the imprinted expression of the retrotransposon-like gene Rtl1 in mice and the orthologous PEG11 gene in sheep and humans [93, 94]. [score:3]
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[+] score: 3
miRNAs for Pik3cg (miR-707), Hbp1 (miR-127, miR-183, and miR-873), Twistnb (miR-718, and miR-691), and Dgkb (miR-489) had no impact on luciferase expression (Figure 2A and data not shown). [score:3]
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[+] score: 3
On the other hand, mutation of Tarbp2 rescued levels of miR-127 and miR145 to wild-type levels, but had no effect on miR-120 and actually resulted in an increase in two miRNAs, let-7e and miR-484, that had been unaffected in wild-type MEFs. [score:2]
The levels of two of the miRNAs, miR-127 and miR145, remained significantly depressed in Prkra [−/−] MEFs, while the levels of one miRNA, miR-120, were rescued, although not to wild-type levels (Figure 4B middle). [score:1]
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[+] score: 3
Onnis A Navari M Antonicelli G Morettini F Mannucci S De FG Vigorito E Leoncini L Epstein-Barr nuclear antigen 1 induces expression of the cellular microRNA hsa-miR-127 and impairing B-cell differentiation in EBV-infected memory B cells. [score:3]
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[+] score: 3
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-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, mmu-mir-128-2, 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
The analysis showed miRNAs that were related to ER stress pathway (let-7f, miR-351, miR-127, miR-133a, miR-195, miR-214 and miR-503), suggesting CASP3, CASP7, XBP1, ATF6 and ATF4 as possible target genes for these miRNAs (Table 4). [score:3]
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[+] score: 3
Notably, microRNAs hsa-miR-127-5p, hsa-miR-370 and hsa-miR-376 had been shown to be highly and specifically expressed in islets of developing and adult human pancreas [53, 54]. [score:3]
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[+] score: 3
Mmu-miR-125b-5p, mmu-miR-34c-5p, mmu-miR-199b-5p, mmu-miR-379-5p, and mmu-miR-127-3p were increased in expression in Sca1 [+]CD31 [−] cells compared to Sca1 [+]CD31 [+] cells. [score:2]
The miRNAs were mmu-miR-125b-5p, mmu-miR-34c-5p, mmu-miR-199b-5p, mmu-miR-379-5p, mmu-miR-127-3p, mmu-miR-322-5p, mmu-miR-20a-5p, mmu-miR-15a-5p, mmu-miR-503-3p, and mmu-miR-204-5p. [score:1]
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60
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Subsequent microRNA microarray screens have identified several microRNA candidates, such as miR-127, as possible players in early lung development [12]. [score:2]
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61
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Other miRNAs from this paper: mmu-mir-24-1, mmu-mir-24-2
MicroRNA-127 promotes mesendoderm differentiation of mouse embryonic stem cells by targeting left-right determination factor 2. J. Biol. [score:2]
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62
[+] score: 1
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-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, mmu-mir-128-2, 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
Of the miRNAs in the porcine Dik1-Dio3 region, there were four annotated miRNAs: ssc-miR-127, ssc-miR-495, ssc-miR-493 and ssc-miR-136. [score:1]
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When a uniform signal was visible across the entire section, the pattern was defined 'ubiquitous' (ubi) (e. g. miR-127 in P0 head and miR-770-3p in P60 eye; Figure 2). [score:1]
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Moreover, the level of miRNA-375, together with miRNA-127-3p and miR-184 is positively correlated to insulin mRNA levels in islets from human donors and the association between these miRNAs and β-cell function was deranged in islets from glucose intolerant donors [18]. [score:1]
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