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24 publications mentioning dre-mir-125b-3

Open access articles that are associated with the species Danio rerio and mention the gene name mir-125b-3. 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: 341
To systematically identify direct targets of miR-125b in the p53 network of vertebrates, we first employed a bioinformatics approach by identifying all predicted miR-125b targets in the p53 network, followed by three complementary methods to screen and validate these targets for both direct binding and repression by miR-125b (Figure 1). [score:9]
Our identification of 20 direct targets of miR-125b in the p53 network reconciles these findings because miR-125b modulates the expression of both apoptosis regulators and cell-cycle regulators. [score:8]
We identified 20 direct targets of miR-125b in the p53 network, including 15 novel targets like Zac1, Puma, Itch and Cdc25c, and also targets like Bak1 and Tp53 that were identified in previous studies [9], [16]– [18]. [score:8]
On the other hand, miR-125b can also downregulate proliferation in a variety of human cancer cell-lines [19]– [23] and one of its bona fide targets Lin28, also promotes cancer cell proliferation [24]. [score:6]
Finally, we checked miR-125b regulation of protein expression in a subset of p53 network targets for which reliable Western blotting was possible. [score:6]
Although miR-125b's suppression of p53 itself is not conserved in mice, miR-125b's anti-apoptotic role – through suppression of multiple pro-apoptosis regulators in the p53 network – appears to be conserved in vertebrates. [score:6]
Quantification of the pulled down mRNA targets in hLF cells revealed that 13 out of 22 gene transcripts, Bak1, Cdc25c, Edn1, Igfbp3, Mre11a, Ppp1ca, Ppp2ca, Prkra, Puma, Tdg, Tp53, Tp53inp1 and Zac1, were direct binding targets of miR-125b in human cells (Figure 3A). [score:6]
In this study, we sought to identify direct targets of miR-125b in the p53 network of humans, mice and zebrafish, to better understand how miR-125b regulates the p53 network throughout evolution and how that might relate to its conserved role in regulating tissue stem cells. [score:6]
We demonstrate that miR-125b directly represses 20 novel targets in the p53 network, including both apoptosis regulators like Bak1, Igfbp3, Itch, Puma, Prkra, Tp53inp1, Tp53, Zac1, and also cell-cycle regulators like cyclin C, Cdc25c, Cdkn2c, Edn1, Ppp1ca, Sel1l. [score:6]
Overexpression of miR-125a/b causes an expansion of mammalian hematopoietic stem cells (HSCs) and aberrant differentiation, leading to myeloid leukemia [9], [10] and also lymphoid leukemia if miR-125b is overexpressed in fetal liver HSC-enriched cells [12]. [score:5]
Transfection of miR-125b significantly suppressed 40-60% (P<0.01) of the luciferase activity of many 3′ UTR reporters of the miR-125b targets we analyzed, relative to transfection of the negative control miRNA (Figure 4A). [score:5]
To address this question, we used a gain- and loss-of-function screen for miR-125b targets in different vertebrates, and validated these targets with the luciferase assay and a novel miRNA-target pull-down assay. [score:5]
miR-125a-AS was co -transfected with miR-125b-AS to achieve a complete silencing of the miR-125a/b family, because miR-125a, which shares the same seed sequence and the same predicted targets as miR-125b, is also highly expressed in human and mouse fibroblasts (Figure S1C, S1D). [score:5]
The genes at the intersection of the predicted miR-125b target list and the list of p53 network genes constituted our list of predicted miR-125b targets in the p53 network (Table S1). [score:5]
Tp53 mRNA was pulled down by miR-125b only in human lung fibroblasts and zebrafish embryos but not in mouse fibroblasts, consistent with previously published results [16] and the Targetscan algorithmic prediction that miR-125b targets Tp53 in humans and zebrafish but not in mice. [score:5]
On the other hand, several research groups have also reported miR-125b's role as a potential tumor suppressor by suppressing proliferation in cell-culture mo dels [19]– [23]. [score:5]
cell-cycle regulators and thus buffer the p53 network dosage in different contexts, could explain why miR-125b dysregulation can lead to either tumor suppression or oncogenesis depending on the context. [score:5]
We then analyzed the TargetScan and MicroCosm Target databases [31], [32] for genes that are predicted to possess miR-125b -binding sites in their 3′ UTRs, in three vertebrate genomes: human, mouse and zebrafish. [score:5]
The targets of miR-125b in human and mouse were predicted by TargetScan [31]. [score:5]
miR-125b has been shown to downregulate apoptosis in many contexts, in some cases by repressing Tp53 and Bak1. [score:4]
Direct binding interactions between miR-125b and mRNA targets from the p53 network. [score:4]
Instead, conserved miR-125b regulation of the p53 network appears to occur through evolving miRNA-target pairs in the three vertebrates – zebrafish (Figure 6A), mouse (Figure 6B), and humans (Figure 6C). [score:4]
To assess which candidate miR-125b targets identified in the gain- and loss-of-function qRT-PCR screen are directly bound by miR-125b in cells, we employed a novel miRNA pull-down method developed by Lal et al. (manuscript in preparation). [score:4]
miR-125b regulation of the p53 network, but not individual miRNA-target pairs, is conserved. [score:4]
As a final validation of the candidate miR-125b targets we have identified in the p53 network, we tested our candidate target genes with the luciferase reporter assay. [score:4]
of point mutations into the predicted seed binding sequences abrogated miR-125b-repression of each target 3′UTR luciferase reporter (P<0.05), validating the predicted miR-125b binding sites and confirming the miRNA-mRNA sequence evolution patterns we observed (Figure 4E). [score:4]
Where cloning was successful, we cloned the entire 3′ UTR of selected candidate target genes into a Renilla luciferase reporter, and assayed luciferase expression following co-transfection of miR-125b duplex into HEK-293T cells. [score:4]
Genes that were either significantly repressed by miR-125b or significantly derepressed by miR-125a/b-AS with fold-changes within the range of microRNA regulation (P<0.05, fold change > 1.3), were selected as candidate miR-125b targets (Figure 2B–2D). [score:4]
Using our conservative estimate of miR-125b targets in the p53 network, we found that in all three vertebrates we examined – humans, mice and zebrafish – miR-125b regulates multiple p53 network genes. [score:4]
Identifying direct targets of miR-125b in the p53 network. [score:4]
Candidate p53 network genes that were positive in both the GOF/LOF screen and miR-125b pull-down were validated for targeting by miR-125b using the 3′ UTR luciferase reporter assay and Western blots for protein expression. [score:4]
In mouse N2A neuroblastoma cells, miR-125b significantly downregulated mouse BAK1, PPP1CA, PUMA, and ITCH protein (Figure 4G). [score:4]
We found that, although each miRNA-target pair evolves rapidly across vertebrates, regulation of the p53 pathway by miR-125b is conserved at the network level. [score:4]
On the other hand, the strict conservation of miR-125b-regulation at the network-level in humans, mice and zebrafish, suggests that natural selection acts on the network-level rather than the gene-level with regard to miRNA-target evolution. [score:4]
Instead, we found that only the network-level of regulation was conserved, and miR-125b-regulation of individual apoptosis and proliferation regulators appears to be evolving rapidly from species to species. [score:4]
In general, we observe miR-125b regulating 2 general classes of genes in the p53 network: (i) apoptosis regulators like Bak1, Igfbp3, Itch, Puma, Prkra, Tp53inp1, Tp53, and Zac1, and (ii) cell-cycle regulators like cyclin C, Cdc25c, Cdkn2c, Edn1, Ppp1ca, and Sel1l. [score:4]
Summary of genes in p53 network that are directly targeted by miR-125b. [score:4]
These studies have ascribed miR-125b's anti-apoptotic effect as an oncogene to its direct suppression of Bak1 or Tp53 [9], [16]- [18]. [score:4]
Figure S1Mature miR-125b levels before and after overexpression or knockdown. [score:4]
miR-125b significantly downregulated the protein levels of human BAK1, PPP1CA, TP53INP1, PPP2CA, CDC25C, and TP53 in SH-SY5Y neuroblastoma cells (Figure 4F). [score:4]
Our results reveal that miR-125b regulation of the p53 network is conserved at the network-level over the course of vertebrate evolution, but individual miRNA-target pairs are evolving rapidly. [score:4]
We found that although individual miRNA-target pairs were seldom conserved, regulation of the p53 network by miR-125b appears to be conserved at the network-level. [score:4]
In general, we found that miR-125b directly represses 2 classes of genes: apoptosis regulators and cell-cycle regulators. [score:4]
Direct binding of miR-125b to p53 network targets. [score:4]
The 2 classes of miR-125b targets in the p53 network, and the incoherent FFL network motifs that we found, may at least partially explain how miR-125b regulates tissue stem cells in vertebrates. [score:4]
In mouse 3T3 cells, 11 out of 13 gene transcripts, Bak1, Hspa5, Itch, Ppp1ca, Ppp2ca, Prkra, Puma, Sel1l, Sp1, Tdg and Tp53inp1, were found to be direct binding targets of miR-125b (Figure 3B). [score:4]
1002242.g004 Figure 4Candidate p53 network genes that were positive in both the GOF/LOF screen and miR-125b pull-down were validated for targeting by miR-125b using the 3′ UTR luciferase reporter assay and Western blots for protein expression. [score:4]
Amongst these targets, we found Ppp1ca, Prkra and Tp53 to be especially interesting from the evolutionary viewpoint, since all 3 vertebrate species possess these 3 genes, but each gene shows a different pattern of evolutionary conservation with respect to miR-125b-repression. [score:3]
However very few individual gene targets of miR-125b in the p53 network were conserved across all three vertebrates (Figure 5; Figure 6A-6C). [score:3]
In mice, out of 22 predicted targets in the p53 network, 11 genes were derepressed by miR-125a/b-AS in 3T3 cells and 12 genes were repressed by miR-125b in N2A cells (Figure 2C). [score:3]
Validation of miR-125b targets in the p53 network. [score:3]
Identifying miR-125b targets in the p53 network of vertebrates. [score:3]
It could explain how overexpression of miR-125b leads to an expansion of self-renewing hematopoietic stem cells while loss of miR-125b leads to aberrant apoptosis and proliferation, with consequent defects in tissue differentiation. [score:3]
For humans, the 3′ UTR reporters of Bak1, Cdc25c, Ppp1ca, Ppp2ca, Prkra, Puma, Tdg, Tp53, Tp53inp1, and Zac1 were significantly suppressed by miR-125b. [score:3]
Fine-regulation of p53 network dosage by miR-125b may also explain miR-125b's conserved role in regulating tissue stem cell homeostasis. [score:3]
Due to the central role of the p53 network in these two processes, and because we found that miR-125b regulates both human and zebrafish Tp53 but not mouse Tp53 [16], we sought to examine if miR-125b regulates the p53 network in a conserved manner in vertebrates. [score:3]
In mice, the 3′ UTR reporters of Bak1, Itch, Ppp1ca, Ppp2ca, Prkra, Puma, Sel1l, Tdg, and Tp53inp1 were significantly suppressed by miR-125b (Figure 4B). [score:3]
In zebrafish, the 3′ UTR reporters of Ccnc, Cdc25c, Cdkn2c, Gtf2h1, Hspa5, Ppp1ca, and Tp53 were significantly suppressed by miR-125b (Figure 4C). [score:3]
The targets of miR-125b in zebrafish were predicted by MicroCosm [32]. [score:3]
Validation of miR-125b targets. [score:3]
By fine-tuning both apoptosis regulators and cell-cycle regulators, miR-125b may fine-tune the p53 network dosage to drive the self-renewal of tissue stem cells. [score:3]
Next we sought to screen our list of predicted targets for significant repression by miR-125b in cells, by performing a miR-125b gain- and loss-of-function screen. [score:3]
Here we describe how miR-125b targets 20 apoptosis and proliferation genes in the p53 network. [score:3]
Prediction of miR-125b targets in the p53 network. [score:3]
Taken together the three assays provide a powerful means to identify direct miR-125b targets. [score:3]
Our GOF/LOF screen revealed that in humans, out of 29 predicted targets in the p53 network, 13 genes were derepressed by miR-125a/b-AS in hLF cells and 20 genes were repressed by miR-125b in SH-SY5Y cells (Figure 2B). [score:3]
In zebrafish embryos, out of 20 predicted targets in the p53 network, 13 genes were derepressed by pre- miR-125b morpholino and 12 genes were repressed by the injection of miR-125b duplex (Figure 2D). [score:3]
To summarize our results, our list of predicted miR-125b targets in the p53 network (Table S1) was filtered and reclassified according to the results of the screen and validation assays (Figure 5). [score:2]
To examine the sequence evolution of these miRNA-mRNA pairs in greater detail, we compared the Targetscan-predicted miR-125b binding sites of these genes in humans, mice and zebrafish. [score:2]
Gain-of-function (GOF) in miR-125b was achieved by transfection of miR-125b duplex into human SH-SY5Y or mouse N2A neuroblastoma cells, whereas loss-of-function (LOF) in miR-125b was achieved in human primary lung fibroblasts or mouse 3T3 fibroblasts by knocking down miR-125b with an antisense (AS) RNA (Figure 2A). [score:2]
In the knockdown experiments, miR-125b morpholinos were injected at 0.75 pmole/embryo (lp125bMO1/2/3 indicates the co-injection of three lp125bMOs, 0.25 pmole each); miR-125b duplex was injected as 37.5 fmole/embryo. [score:2]
We believe these findings on miR-125b support a new fundamental principle for how miRNAs regulate gene networks in general. [score:2]
Depending on the cell context, miR-125b has been proposed to regulate both apoptosis and proliferation. [score:2]
The structure of the miR-125b regulatory network suggests that miR-125b buffers and fine-tunes p53 network activity. [score:2]
Predicted targets that passed 3 assays (red), 2 assays (orange), 1 assay (yellow), or predicted targets that failed all assays but whose orthologues in other species passed 3 assays of direct regulation by miR-125b (pink), were colored as indicated (Figure 5). [score:2]
Therefore in different contexts, miR-125b appears to be able to regulate both apoptosis and proliferation. [score:2]
It is possible that this buffering feature of miR-125b represents a general principle of miRNA regulation of gene networks. [score:2]
GOF/LOF screen for p53 network genes regulated by miR-125b. [score:2]
Mo dels of miR-125b regulation of p53 networks in humans, mice, and zebrafish. [score:2]
This shows that miR-125b regulation of the p53 network is conserved at least at the network level. [score:2]
This buffering feature of miR-125b has implications for our understanding of how miR-125b regulates oncogenesis and tissue stem cell homeostasis. [score:2]
The gain-of-function (GOF) screen was performed by co-injecting miR-125b duplex with the morpholino (Figure 2A). [score:1]
The enrichment of mRNAs bound to miR-125b is presented as mean log [2] fold change ± s. e. m. (n≥3 biological replicates). [score:1]
miR-125b gain- and loss-of-function screen in 3 vertebrates. [score:1]
In zebrafish embryos, 8 out of 14 gene transcripts, Cdc25c, Cdkn2c, Gtf2h1, Hspa5, Itch, Ppp1ca, Sel1l, and Tp53, were pulled down by miR-125b (Figure 3C). [score:1]
1002242.g003 Figure 3Biotinylated miR-125b was used as bait to pull-down mRNAs bound to miR-125b, using streptavidin-conjugated magnetic beads. [score:1]
This led us to propose that miR-125b buffers and fine-tunes p53 network dosage, with implications for the role of miR-125b in tissue stem cell homeostasis and oncogenesis. [score:1]
Biotinylated miR-125b was used as bait to pull-down mRNAs bound to miR-125b, using streptavidin-conjugated magnetic beads. [score:1]
Our findings suggest that the fine-tuning of p53 network dosage by miR-125b is another example of this paradigm. [score:1]
Existing databases and prediction algorithms were used to shortlist a set of p53 network genes predicted to possess miR-125b -binding sites in their 3′ UTRs. [score:1]
For zebrafish embryos, which possess high levels of miR-125b, the loss-of-function (LOF) screen was performed using an antisense morpholino cocktail that blocks the loop regions of all 3 pre- miR-125b hairpin precursors [16]. [score:1]
RNA transcripts bound to biotinylated-miR-125b were pulled down with streptavidin beads and quantified by qRT-PCR relative to mRNAs bound to biotinylated-control miRNA (log [2] fold change > 0.5, P<0.05). [score:1]
Our observation that an incoherent FFL-like network motif fits the overall structure of the miR-125b - p53 network mo dels with respect to apoptosis and cell proliferation, lends further support to this idea since incoherent FFL network motifs are well-adapted for noise filtering [41], [43], [46]. [score:1]
With the exception of zebrafish Ccnc, all genes tested were positive in the miR-125b-pull-down as well as the miR-125b gain- and loss-of-function screen. [score:1]
A reporter containing a 23-nucleotide -binding-site with perfect complementarity to miR-125b was used as the perfect match positive control, while the unmodified luciferase reporter was used as the empty negative control. [score:1]
In all panels, the levels of miR-125a and miR-125b were quantified by real-time PCR, and presented as log [2] (fold change) ± s. e. m. (n≥3) relative to the levelsof RNU6B loading control. [score:1]
Several studies have implicated miR-125b as an oncogene in a variety of mammalian tissue compartments, e. g. leukemia, neuroblastoma, prostate cancer and breast cancer [9]– [18]. [score:1]
hsa-miR-125b or cel-miR-67 (negative control) duplex was synthesized with a biotin conjugated at the 3′ end of the active strand by Dharmacon Research Inc. [score:1]
1002242.g002 Figure 2(A) Loss-of-function (LOF) screens were performed in human primary lung fibroblasts (hLF) or mouse 3T3 fibroblasts by transfecting an antisense RNA against both miR-125a and miR-125b (miR-125a/b-AS), or by microinjecting morpholinos (MO) against pre- mir-125b hairpin precursors (all 3 isoforms) into zebrafish embryos. [score:1]
Ppp1ca is repressed by miR-125b in all 3 species, Prkra is repressed by miR-125b in humans and mice, while Tp53 is repressed in humans and zebrafish. [score:1]
We chose to perform a gain-of-function screen in human (SH-SY5Y) or mouse (N2A) neuroblastoma cells, because these cells possess low levels of endogenous miR-125b (Figure S1A, S1B). [score:1]
From the GOF/LOF screen we were able to identify mRNAs perturbed by miR-125b. [score:1]
During zebrafish embryogenesis, loss of miR-125b leads to widespread apoptosis in a p53 -dependent manner, causing severe defects in neurogenesis and somitogenesis [16]. [score:1]
Gain-of-function (GOF) screens were performed in human SH-SY5Y and mouse N2A neuroblastoma by transfecting the miR-125b duplex into cells in culture, or by coinjecting the miR-125b duplex with the morpholinos against pre- mir-125b into zebrafish embryos. [score:1]
In other words, the loss or gain of a single miR-125b -binding site in the 3′ UTR of most genes appears to have a relatively insignificant effect on the fitness of an organism. [score:1]
For the loss-of-function screen, we chose human fetal lung (hLF) or mouse (3T3) fibroblasts because they possess high levels of miR-125b (Figure S1C, S1D). [score:1]
miR-125b's ability to fine-tune the subtle balance of apoptosis vs. [score:1]
Because miR-125b represses both pro-apoptosis and anti-apoptosis genes, as well as both proliferation and cell-cycle arrest genes in all three vertebrates (Figure 5), miR-125b appears to modulate the p53 network on the whole through an incoherent feedforward loop (FFL) [33], [34] acting on the cellular processes of apoptosis and cell proliferation (Figure 6D). [score:1]
Thus our finding that incoherent FFLs fit the overall structure of network relationships between miR-125b and the p53 -mediated processes, suggests that miR-125b is fine-tuning and buffering p53 network dosage. [score:1]
In zebrafish, loss of miR-125b leads to widespread p53 -dependent apoptosis with consequent defects in early embryogenesis, especially in neurogenesis and somitogenesis [16]. [score:1]
Table S1Genes in p53 network with predicted miR-125b binding sites. [score:1]
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[+] score: 58
Since zebrafish lin-28b and lin-41 have a lin-4/miR-125b and let-7 target sites in their 3′UTRs (using Targetscan and PITA) [33], the downregulation of lin-28b and lin-41 might be directly regulated by these miRNAs. [score:10]
On the other hand, the expression of let-7 and lin-4/miR-125b miRNA, a downstream heterochronic gene of lin-28, was expressed subsequent to lin-28b expression. [score:7]
In the C. elegans heterochronic pathway, let-7 and lin-4/miR-125 miRNA play an essential regulatory role in the timing of stage-specific cell lineage development in nematodes, in part by directly regulating their target genes [5], [6], [13], [14]. [score:7]
Concomitant with the increased expression of let-7 and lin-4/miR-125b, the expression of lin-28b and lin-41 began to decrease from 24 and 48 hpf, respectively (Figure 6B). [score:5]
Interestingly, consistent with decreased lin-28a and lin-28b expression, let-7a, let-7b, and lin-4/miR125b miRNA expression was dramatically increased at 72 hpf (Figure 2B). [score:5]
Lin-28a and Lin-28b Regulate the Expression of Downstream Heterochronic Genes, as well as the miR-430 miRNA familyIn the C. elegans heterochronic pathway, miRNAs, including let-7 and lin-4/miR-125, play a critical role as downstream genes of lin28. [score:4]
On the other hand, let-7 and miR-125 are reportedly expressed in a reciprocal fashion to Lin28a and Lin41 during mouse development [36], [39] (Figure 6C). [score:4]
For example, let-7 and lin-4/miR-125 are highly conserved and expressed in various species, including Drosophila and humans [20], [34], [35]. [score:3]
To characterize the expression pattern of zebrafish homologs of heterochronic genes (including lin-28, let-7, lin-41/TRIM71, and lin-4/miR-125b) in zebrafish development, reverse transcription-PCR (RT-PCR), TaqMan quantitative RT-PCR (qRT-PCR), and whole-mount in situ hybridization were performed on embryos at various developmental stages. [score:3]
B. Real-time PCR analysis of let-7a, let-7b and lin-4/miR-125b miRNA expression. [score:3]
Expression levels of let-7a, let-7b and lin-4/miR-125b was analyzed using TaqMan miRNA assay. [score:2]
Moreover, lin-41 and lin-28 are highly conserved in mammals and are regulated by let-7 and miR-125 like C. elegans [22], [36]. [score:2]
For example, in has been suggested that Lin28, let-7 and miR125 play important roles in cell fate determination in ES cells [24]. [score:1]
In the C. elegans heterochronic pathway, miRNAs, including let-7 and lin-4/miR-125, play a critical role as downstream genes of lin28. [score:1]
For example, lin-4/miR-125 miRNA promotes the transition between the first and second larval stages (L1 and L2, respectively) by binding to complementary sites in the 3′UTR of the upstream heterochronic genes lin-14 and lin-28 [3], [6], [15]– [17]. [score:1]
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[+] score: 41
In addition, miR-125b is known to targets p53 mRNA to regulate embryonic development and stress response in zebrafish [46]. [score:5]
In summary, we show that over expression of miR-125b resulted a corresponding decrease in the expression levels of the predicted 7sl lncRNA in zebrafish embryos. [score:5]
Ectopic overexpression of miR-125b (10 µM) resulted in anterior-posterior axis curvature defects in approximately 80% of the injected zebrafish embryos at 2 dpf (n = 225/283) (Figure 3C and 3D). [score:3]
The predicted miR-125b target region is highlighted in gray color. [score:3]
For overexpression of miR-125b mimic (Dharmacon), two to three nanoliter (nl) containing 10 µM miRNA mimic was injected at one cell stage zebrafish embryos. [score:3]
0053823.g003 Figure 3 7sl RNA lncRNA is down regulated by mir-125b in Zebrafish. [score:2]
7sl RNA lncRNA is down regulated by mir-125b in Zebrafish. [score:2]
Prior to examining the interaction of miR-125b with the predicted 7sl lncRNA in developing zebrafish embryos, we investigated the expression of the predicted zebrafish 7sl lncRNA during zebrafish embryonic development using reverse transcriptase PCR technique. [score:2]
Further expression of the predicted 7sl lncRNA was assayed in miR-125b injected embryos using quantitative real-time PCR. [score:2]
MiR-125b is known to express ubiquitously during zebrafish embryogenesis [46]. [score:2]
7sl RNA lncRNA is Down Regulated by mir-125b in Zebrafish. [score:2]
The interaction of miR-125b and 7sl lncRNA was investigated by ectopic overexpression of miR-125b mimic in zebrafish embryos [47]. [score:1]
MiR-125b injected embryos displayed reduction in expression of the predicted 7sl lncRNA by approximately 1.72 fold (0.42±0.26 SD) compared to non -injected embryos (NIC) (Figure 3E). [score:1]
In addition, we have experimentally validated the interaction of 7sl lncRNA with miR-125b in a zebrafish mo del, thus adding confidence to our hypothesis. [score:1]
0053823.g002 Figure 2 The figure shows predicted binding alignment of miR-125a, miR-125b, miR-125c, miR-17a*, miR-20*, miR-210*, miR-29a, miR-29b and miR457a with predicted zebrafish lncRNA. [score:1]
The figure shows predicted binding alignment of miR-125a, miR-125b, miR-125c, miR-17a*, miR-20*, miR-210*, miR-29a, miR-29b and miR457a with predicted zebrafish lncRNA. [score:1]
Therefore, we were intrigued to study the interaction of miR-125b with the predicted 7sl lncRNA in developing zebrafish embryos. [score:1]
The miRanda software identified potential binding sites of miR-125a, miR-125b, miR-125c, miR-17a*, miR-20a*, miR-210*, miR-2187, miR-29a, miR-29b and miR-457a in the predicted zebrafish 7sl lncRNA (Figure 2). [score:1]
Non -injected control (NIC), control mimic (miR-144) and miR-125b mimic. [score:1]
B: Predicted binding alignment of miR-125b with human 7sl lncRNA and the predicted zebrafish lncRNA. [score:1]
C) Non -injected control embryo (NIC) and D) miR-125b injected embryo. [score:1]
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[+] score: 36
Evidences demonstrated that, in some cases, miR-125 could directly downregulate p53 and further influence the downstream protein p21 which is a CDK inhibitor [61, 62]. [score:7]
Based on TargetScan bioinformatic algorithm, zebrafish p53 was also identified as a potential target of miR-125 with a putative binding site on the 3′UTR, which is not verified in the current study but provides a new direction for the follow-up study. [score:6]
MiR-125 family is highly conserved throughout evolution, and it was demonstrated to regulate tumorigenesis and tumor development by targeting important genes including transcription factors like CBFB and TGF-β [52, 53], anti-apoptotic genes like BCL2, BCL2L12 and Mcl-1 [54], pro-apoptotic protein Bak1 [55], and tumor suppressing protein p53 [55, 56]. [score:6]
Recent studies have exhibited the dual function of miR-125 family as tumor suppressor and promotor, and the aberrant expression of miR-125 family is tightly related to tumorigenesis [43, 44]. [score:5]
Both miR-125a and miR-125b play excellent roles in the zebrafish brain development [67], meanwhile miR-125b also regulates the zebrafish eye development [67]. [score:4]
It was reported that miR-125 family has a dual function in suppression and promotion of cancer cells [44]. [score:3]
Interestingly, we identified a putative binding site of miR-125 on zebrafish cdc25a 3′UTR by TargetScan, which is absent on the CDC25A 3′UTR of both human and mouse. [score:3]
Recently, miR-125 has been confirmed to be hypoxia -induced in human cancer cells [7], also it was demonstrated to function in the transgenerational effect of hypoxia in medaka testis [48]. [score:1]
The miR-125 family, a highly conserved miRNA family throughout evolution, has been demonstrated to be implicated in a variety of physiological processes, including cell proliferation and apoptosis [39, 40], cell metastasis [41] and immune response [42]. [score:1]
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As regards IR -induced miRNA expression, a significant down-regulation of miR-125b expression was found in zebrafish embryos in response to IR -induced DNA damages, which led to a rapid increase in p53 protein [241]. [score:8]
A significant down-regulation of miR-125b expression was found in zebrafish embryos in response to IR -induced DNA damages, which resulted in a rapid increase in p53 protein [241]. [score:6]
On the other hand, miR-125b, one of the miRNAs, was shown to directly regulate p53 in zebrafish and in human cells [241]. [score:3]
Accordingly, Le et al. suggested that miR-125b -mediated regulation of p53 was critical for modulating apoptosis in human cells as well as in zebrafish embryos exposed to IRs [241]. [score:2]
Le M. T. The C. Shyh-Chang N. Xie H. Zhou B. Korzh V. Lodish H. F. Lim B. MicroRNA-125b is a novel negative regulator of p53 Genes Dev. [score:1]
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[+] score: 11
It is tempting to speculate that the miR-125 family—the mammalian homolog of the C. elegans heterochronic miRNA lin-4-is also targeted by Zcchc11 and Zcchc6 due to its known role in development, yet the mechanism of this targeting remains unknown. [score:6]
Interestingly, miR-125 family members are expressed from some of these same genomic clusters but do not contain the predicted targeting sequence. [score:5]
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7
[+] score: 10
Likewise, miRNAs can be regulated by many genes; among them some specific miRNAs could be regulated via MOR, where fentanyl downregulates miR-190 [17], [18] and morphine decreases miRNAs such as miR-28, miR-125b, miR-150, and miR-382 [19]. [score:6]
Fentanyl downregulates miR-190 in hippocampal neuron cultures [17], [18] and morphine decreases miRNAs such as miR-28, miR-125b, miR-150, and miR-382 in monocytes [19]. [score:4]
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8
[+] score: 6
Inhibition of three miRNAs, let-7, miR-125, and miR-9, caused similar defects in retinal development shown in Dicer1 conditional knock-out mice, further confirming that miRNAs are essential for early retinal development [23]. [score:6]
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9
[+] score: 6
Other miRNAs from this paper: dre-mir-10a, dre-mir-10b-1, dre-mir-204-1, dre-mir-181a-1, dre-mir-214, dre-mir-222a, dre-mir-430a-1, dre-mir-430b-1, dre-mir-430c-1, dre-let-7a-1, dre-let-7a-2, dre-let-7a-3, dre-let-7a-4, dre-let-7a-5, dre-let-7a-6, dre-let-7b, dre-let-7c-1, dre-let-7c-2, dre-let-7d-1, dre-let-7d-2, dre-let-7e, dre-let-7f, dre-let-7g-1, dre-let-7g-2, dre-let-7h, dre-let-7i, dre-mir-10b-2, dre-mir-10c, dre-mir-10d, dre-mir-17a-1, dre-mir-17a-2, dre-mir-21-1, dre-mir-21-2, dre-mir-22a, dre-mir-22b, dre-mir-25, dre-mir-26a-1, dre-mir-26a-2, dre-mir-26a-3, dre-mir-30d, dre-mir-92a-1, dre-mir-92a-2, dre-mir-92b, dre-mir-100-1, dre-mir-100-2, dre-mir-125a-1, dre-mir-125a-2, dre-mir-125b-1, dre-mir-125b-2, dre-mir-125c, dre-mir-126a, dre-mir-143, dre-mir-146a, dre-mir-462, dre-mir-202, dre-mir-204-2, dre-mir-430c-2, dre-mir-430c-3, dre-mir-430c-4, dre-mir-430c-5, dre-mir-430c-6, dre-mir-430c-7, dre-mir-430c-8, dre-mir-430c-9, dre-mir-430c-10, dre-mir-430c-11, dre-mir-430c-12, dre-mir-430c-13, dre-mir-430c-14, dre-mir-430c-15, dre-mir-430c-16, dre-mir-430c-17, dre-mir-430c-18, dre-mir-430a-2, dre-mir-430a-3, dre-mir-430a-4, dre-mir-430a-5, dre-mir-430a-6, dre-mir-430a-7, dre-mir-430a-8, dre-mir-430a-9, dre-mir-430a-10, dre-mir-430a-11, dre-mir-430a-12, dre-mir-430a-13, dre-mir-430a-14, dre-mir-430a-15, dre-mir-430a-16, dre-mir-430a-17, dre-mir-430a-18, dre-mir-430i-1, dre-mir-430i-2, dre-mir-430i-3, dre-mir-430b-2, dre-mir-430b-3, dre-mir-430b-4, dre-mir-430b-6, dre-mir-430b-7, dre-mir-430b-8, dre-mir-430b-9, dre-mir-430b-10, dre-mir-430b-11, dre-mir-430b-12, dre-mir-430b-13, dre-mir-430b-14, dre-mir-430b-15, dre-mir-430b-16, dre-mir-430b-17, dre-mir-430b-18, dre-mir-430b-5, dre-mir-430b-19, dre-mir-430b-20, dre-let-7j, dre-mir-181a-2, dre-mir-1388, dre-mir-222b, dre-mir-126b, dre-mir-181a-4, dre-mir-181a-3, dre-mir-181a-5, dre-mir-204-3
The most enriched GO term was segment polarity determination (GO:0007367), which contained target mRNA for the miR-10 and miR-125 families, as well as miR-181a-5p miR-21-5p, miR-222a-3p, and miR-430b-3p. [score:3]
Of the testis-enriched miRNAs, the let-7 family was well represented at 6 wpf (Fig. 6a), while the miR-125 family was abundant at 6, 9, and 24 wpf (Fig. 6a,b,d). [score:1]
Our findings were similar to deep sequencing results in mature zebrafish gonads, which also reported higher abundance of 125a-5p, miR-125b-5p, miR-125c-5p, and miR-462-5p in the testis, although that study did not find higher abundance of miR-22a-3p in the ovaries 27. [score:1]
Several miRNAs were consistently more abundant in testis than ovary, including miR-125a-5p, miR-125b-5p, miR-125c-5p, and miR-462-5p, whereas miR-22a-3p and miR-430b-3p were more abundant in the ovary (Fig. 6). [score:1]
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10
[+] score: 6
It has been demonstrated that miR-125b is an important negative regulator of p53 and p53 -induced apoptosis during development as well as in stress response [25]. [score:3]
In the present studies, expression changes in miR-430 and miR-125 families were quite significant. [score:3]
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11
[+] score: 3
Data were normalized to abundance of miR-125b mRNA and expressed as relative fold change using the sample with the lowest value as the calibrator (mean ± SEM; n = 4 pools of five oocytes/embryos each). [score:3]
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12
[+] score: 3
Combination wt-p53 and microRNA-125b transfection in a genetically engineered lung cancer mo del using dual CD44/EGFR -targeting nanoparticles. [score:3]
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13
[+] score: 3
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-18a, hsa-mir-21, hsa-mir-27a, hsa-mir-96, hsa-mir-99a, mmu-let-7g, mmu-let-7i, mmu-mir-27b, mmu-mir-30b, mmu-mir-99a, mmu-mir-124-3, mmu-mir-125b-2, mmu-mir-9-2, mmu-mir-135a-1, mmu-mir-181a-2, mmu-mir-182, mmu-mir-183, mmu-mir-199a-1, hsa-mir-199a-1, mmu-mir-200b, hsa-mir-181a-2, hsa-mir-182, hsa-mir-183, hsa-mir-199a-2, hsa-mir-181a-1, hsa-mir-200b, mmu-let-7d, hsa-let-7g, hsa-let-7i, hsa-mir-27b, hsa-mir-30b, hsa-mir-124-1, hsa-mir-124-2, hsa-mir-124-3, hsa-mir-125b-1, hsa-mir-135a-1, hsa-mir-135a-2, hsa-mir-9-1, hsa-mir-9-2, hsa-mir-9-3, hsa-mir-125b-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-15a, mmu-mir-18a, mmu-mir-21a, mmu-mir-27a, mmu-mir-96, mmu-mir-135b, mmu-mir-181a-1, mmu-mir-199a-2, mmu-mir-135a-2, mmu-mir-124-1, mmu-mir-124-2, mmu-mir-9-1, mmu-mir-9-3, mmu-mir-125b-1, hsa-mir-200a, hsa-mir-135b, dre-mir-182, dre-mir-183, dre-mir-181a-1, dre-let-7a-1, dre-let-7a-2, dre-let-7a-3, dre-let-7a-4, dre-let-7a-5, dre-let-7a-6, dre-let-7b, dre-let-7c-1, dre-let-7c-2, dre-let-7d-1, dre-let-7d-2, dre-let-7e, dre-let-7f, dre-let-7g-1, dre-let-7g-2, dre-let-7h, dre-let-7i, dre-mir-9-1, dre-mir-9-2, dre-mir-9-4, dre-mir-9-3, dre-mir-9-5, dre-mir-9-6, dre-mir-9-7, dre-mir-15a-1, dre-mir-15a-2, dre-mir-18a, dre-mir-21-1, dre-mir-21-2, dre-mir-27a, dre-mir-27b, dre-mir-27c, dre-mir-27d, dre-mir-27e, dre-mir-30b, dre-mir-96, dre-mir-124-1, dre-mir-124-2, dre-mir-124-3, dre-mir-124-4, dre-mir-124-5, dre-mir-124-6, dre-mir-125b-1, dre-mir-125b-2, dre-mir-135c-1, dre-mir-135c-2, dre-mir-200a, dre-mir-200b, dre-let-7j, dre-mir-135b, dre-mir-181a-2, dre-mir-135a, mmu-mir-21b, mmu-let-7j, mmu-mir-21c, mmu-let-7k, dre-mir-181a-4, dre-mir-181a-3, dre-mir-181a-5, mmu-mir-9b-2, mmu-mir-124b, mmu-mir-9b-1, mmu-mir-9b-3
Despite the relatively moderate differences (15–40%), miRNAs that had the highest differential expression were let-7a, -7b, miR-220, -423, -190, -204,-24, -195 and miR-125b. [score:3]
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[+] score: 3
Other miRNAs from this paper: dre-mir-7b, dre-mir-7a-1, dre-mir-7a-2, dre-mir-34a, dre-mir-181b-1, dre-mir-181b-2, dre-mir-182, dre-mir-183, dre-mir-181a-1, dre-mir-219-1, dre-mir-219-2, dre-mir-221, dre-mir-222a, dre-mir-430a-1, dre-mir-430b-1, dre-mir-430c-1, dre-let-7a-1, dre-let-7a-2, dre-let-7a-3, dre-let-7a-4, dre-let-7a-5, dre-let-7a-6, dre-let-7b, dre-let-7c-1, dre-let-7c-2, dre-let-7d-1, dre-let-7d-2, dre-let-7e, dre-let-7f, dre-let-7g-1, dre-let-7g-2, dre-let-7h, dre-let-7i, dre-mir-7a-3, dre-mir-9-1, dre-mir-9-2, dre-mir-9-4, dre-mir-9-3, dre-mir-9-5, dre-mir-9-6, dre-mir-9-7, dre-mir-92b, dre-mir-96, dre-mir-100-1, dre-mir-100-2, dre-mir-124-1, dre-mir-124-2, dre-mir-124-3, dre-mir-124-4, dre-mir-124-5, dre-mir-124-6, dre-mir-125b-1, dre-mir-125b-2, dre-mir-128-1, dre-mir-128-2, dre-mir-132-1, dre-mir-132-2, dre-mir-135c-1, dre-mir-135c-2, dre-mir-137-1, dre-mir-137-2, dre-mir-138-1, dre-mir-153a, dre-mir-181c, dre-mir-200a, dre-mir-218a-1, dre-mir-218a-2, dre-mir-219-3, dre-mir-375-1, dre-mir-375-2, dre-mir-454a, dre-mir-430c-2, dre-mir-430c-3, dre-mir-430c-4, dre-mir-430c-5, dre-mir-430c-6, dre-mir-430c-7, dre-mir-430c-8, dre-mir-430c-9, dre-mir-430c-10, dre-mir-430c-11, dre-mir-430c-12, dre-mir-430c-13, dre-mir-430c-14, dre-mir-430c-15, dre-mir-430c-16, dre-mir-430c-17, dre-mir-430c-18, dre-mir-430a-2, dre-mir-430a-3, dre-mir-430a-4, dre-mir-430a-5, dre-mir-430a-6, dre-mir-430a-7, dre-mir-430a-8, dre-mir-430a-9, dre-mir-430a-10, dre-mir-430a-11, dre-mir-430a-12, dre-mir-430a-13, dre-mir-430a-14, dre-mir-430a-15, dre-mir-430a-16, dre-mir-430a-17, dre-mir-430a-18, dre-mir-430i-1, dre-mir-430i-2, dre-mir-430i-3, dre-mir-430b-2, dre-mir-430b-3, dre-mir-430b-4, dre-mir-430b-6, dre-mir-430b-7, dre-mir-430b-8, dre-mir-430b-9, dre-mir-430b-10, dre-mir-430b-11, dre-mir-430b-12, dre-mir-430b-13, dre-mir-430b-14, dre-mir-430b-15, dre-mir-430b-16, dre-mir-430b-17, dre-mir-430b-18, dre-mir-430b-5, dre-mir-430b-19, dre-mir-430b-20, dre-let-7j, dre-mir-181a-2, dre-mir-34b, dre-mir-34c, dre-mir-222b, dre-mir-138-2, dre-mir-181a-4, dre-mir-181a-3, dre-mir-181a-5, dre-mir-181b-3, dre-mir-181d, dre-mir-128-3
Other miRNAs with expression in the retina include miR-454a (Figure C in5), miR-132 (Figure E in5), miR-125b (Figure F in5) and miR-181a (Figure G in3). [score:3]
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15
[+] score: 3
In mouse, miR-125 is highly expressed in hematopoietic stem cells (HSCs) to expand HSC numbers in vivo [21]. [score:3]
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16
[+] score: 2
Other miRNAs from this paper: hsa-mir-125b-1, hsa-mir-125b-2, dre-mir-125b-1, dre-mir-125b-2
Lu YC CFTR mediates bicarbonate -dependent activation of miR-125b in preimplantation embryo developmentCell Res. [score:2]
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17
[+] score: 2
Northern blot of miR-125 mature sequence expression obtained upon biogenesis assay of miR-125-a1, -a2, -b1, -b2 and -b3 mutants and wild type pri-miRNA genes (bottom). [score:2]
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[+] score: 2
MiR-125b protects against ethanol -induced apoptosis in neural crest cells and mouse embryos by targeting Bak 1 and PUMA. [score:2]
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[+] score: 2
Other miRNAs from this paper: dre-mir-125b-1, dre-mir-125b-2
However, Oct4 has also been linked to survival and anti-apoptotic pathways in ES cells by several different potential mechanisms: by a STAT3/Survivin route [61], by Trp53 regulation [62], or by a miR-125b pathway [63]. [score:2]
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20
[+] score: 2
As was similarly noted for lin-41 in C. elegans, Mlin41 also appears to be regulated by the let-7 and mir-125 miRNAs. [score:2]
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21
[+] score: 1
Quantity of miRNA was normalized relative to abundance of miR-125b. [score:1]
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22
[+] score: 1
miRNAs let-7a, miR-100-5p, miR-10b-5p, miR-125b-5p, miR-146a, miR-181a-5p, miR-21, miR-27c-3p and miR-92a-3p were the most abundant miRNAs (>100,000 reads) in the four samples (Excel S1). [score:1]
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23
[+] score: 1
The role of microRNAs in lower vertebrates with a known regenerative ability is gaining a lot of attention, with several recent studies identifying miRNAs associated with spinal cord repair (e. g., miR-125b in axolotl, miR-133b in zebrafish; [28, 29]) and appendage regeneration (e. g. miR-196 in axolotl tail, miR-203 in zebrafish fin; [30, 31]). [score:1]
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24
[+] score: 1
Likewise, miR-1, miR-124, miR-125b, miR-132, bantam, miR-34 and the miR-310 cluster have all been implicated in the modulation of synaptic homeostasis [70]– [76]. [score:1]
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