Foshay KM, Gallicano GI... MiR-17 family miRNAs are expressed during early mammalian development and regulate stem cell differentiation. Dev Biol 326: 431-443

Department of Biochemistry and Molecular & Cellular Biology, Georgetown University Medical Center, Washington, DC 20007, USA.
Developmental Biology (Impact Factor: 3.55). 02/2009; 326(2):431-43. DOI: 10.1016/j.ydbio.2008.11.016
Source: PubMed


MicroRNAs are small non-coding RNAs that regulate protein expression by binding 3'UTRs of target mRNAs, thereby inhibiting translation. Similar to siRNAs, miRNAs are cleaved by Dicer. Mouse and ES cell Dicer mutants demonstrate that microRNAs are necessary for embryonic development and cellular differentiation. However, technical obstacles and the relative infancy of this field have resulted in few data on the functional significance of individual microRNAs. We present evidence that miR-17 family members, miR-17-5p, miR-20a, miR-93, and miR-106a, are differentially expressed in developing mouse embryos and function to control differentiation of stem cells. Specifically, miR-93 localizes to differentiating primitive endoderm and trophectoderm of the blastocyst. We also observe high miR-93 and miR-17-5p expression within the mesoderm of gastrulating embryos. Using an ES cell model system, we demonstrate that modulation of these miRNAs delays or enhances differentiation into the germ layers. Additionally, we demonstrate that these miRNAs regulate STAT3 mRNA in vitro. We suggest that STAT3, a known ES cell regulator, is one target mRNA responsible for the effects of these miRNAs on cellular differentiation.

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    • "This effect was particularly observed in female, though did not reach statistical significance after Bonferroni correction (Xie et al., 2013). This SNP is located on 3'-untranslated region (UTR) in STAT3 gene which is the binding site of targeted mRNAs and regulates the expression of STAT3 protein by mRNA degradation (Foshay and Gallicano, 2009; Xie et al., 2013). However, the mechanism by which the SNP contributes to the function of STAT3 protein is not well defined. "
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    ABSTRACT: The single nucleotide polymorphism (SNP) rs1053004 in Signal transducer and activator of transcription 3 (STAT3) was recently reported to be associated with chronic hepatitis B (CHB)-related hepatocellular carcinoma (HCC) in a Chinese cohort. This study was aimed at investigating whether the SNP might also contribute to HCC susceptibility in the Thai population. Study subjects were enrolled and divided into 3 groups including CHB-related HCC (n=211), CHB without HCC (n=233) and healthy controls (n=206). The SNP was genotyped using allelic discrimination assays based on TaqMan real-time PCR. Data analysis revealed that the distribution of different genotypes was in Hardy-Weinberg equilibrium (P>0.05). The frequencies of allele T (major allele) in HCC patients, CHB patients and healthy controls were 51.4%, 58.6% and 61.4%, respectively, whereas the frequencies of C allele (minor allele) were 48.6%, 41.4% and 38.6%. The C allele frequency was higher in HCC when compared with CHB patients (odds ratio (OR)=1.34, 95% confidence interval (CI)=1.02-1.74, P=0.032). The genotype of SNP rs1053004 (CC versus TT+TC) was significantly associated with an increased risk when compared with CHB patients (OR=1.83, 95% CI=1.13-2.99, P=0.015). In addition, we observed a similar trend of association when comparing HCC patients with healthy controls (OR=1.77, 95% CI=1.07-2.93, P=0.025) and all controls (OR=1.81, 95% CI=1.19-2.74, P=0.005). These findings suggest that the SNP rs1053004 in STAT3 might contribute to HCC susceptibility and could be used as a genetic marker for HCC in the Thai population.
    Asian Pacific journal of cancer prevention: APJCP 07/2015; 16(12):5069-5073. DOI:10.7314/APJCP.2015.16.12.5069 · 2.51 Impact Factor
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    • "We found that hsa-miR-181a-3p, hsa- miR-181a-2-3p, hsa-miR-181b-5p, hsa-miR-181b-3p, hsa-miR-181c- 5p, hsa-miR-181c-3p and hsa-miR-181d-5p were up-regulated. Also, almost all the members of the let-7 and miR-449 families are involved in differentiation (Ding et al., 2008; Foshay and Gallicano, 2009; Lize et al., 2011), and they were only expressed at high levels at stages 3–4. Hsa-miR-125b-5p, hsa-miR-125b-1-3p and hsa-miR-125b-2-3p were also expressed at high levels at stages 3–4. "
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    ABSTRACT: Embryonic stem cells (ESCs) and induced pluripotent stem cells can be induced to differentiate into retinal pigment epithelium (RPE). miRNAs have been characterized and found playing important roles in the differentiation process of ESCs, but their length and sequence heterogeneity (isomiRs), and their non-canonical forms of miRNAs are underestimated or ignored. In this report, we found some non-canonical miRNAs (dominant isomiRs) in all differentiation stages, and 27 statistically significant editing sites were identified in 24 different miRNAs. Morever, we found marked major-to-minor arm-switching events in 14 pre-miRNAs during the hESC to RPE cell differentiation phases. Our study for the first time reports exploring the variability of miRNA expression during the differentiation of hESCs into RPE cells and the results show that miRNA variability is a ubiquitous phenomenon in the ESC differentiation. Copyright © 2015. Published by Elsevier B.V.
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    • "MiRNAs are approximately 21-nucleotide small RNAs that are derived from hairpin precursors, which repress protein expression by targeting 3’-UTR (3’-untranslated region) of mRNAs [14]. The miR-17 family consists of six members (miR-17, miR-20a, miR-20b, miR-93, miR-106a and miR-106b), which distribute in three genome clusters [15]. Unlike the miR-17-92 and miR-106b-25 cluster, which are both abundantly expressed in many sorts of tissues, the miR-106a-363 cluster is undetectable or unexpressed in most of the tissues [16,17]. "
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    ABSTRACT: Bone morphogenetic protein (BMP) signaling is active in many tissues including the central nervous system, in which it regulates cell proliferation, differentiation and maturation. The modulation of BMP pathway is crucial since abnormality of BMP signaling may cause cellular malfunction such as apoptosis. There are evidences indicating that miR-17 family is involved in the BMP signaling. In the present study, we demonstrated that BMP2 stimulation directly increased the transcription of miR-17-92 and miR-106b-25 cluster via Smad activation, which leads to the up-regulation of mature miR-17/20a/93. In addition, we provided evidence that BMP2 activation repressed BMPRII expression through modulating miR-17 family in primary neurons. Furthermore, we proved that such negative regulation protected neurons from apoptosis induced by abnormal BMP signaling. Taken together, these results suggest a regulatory pathway of BMP-miR-17 family-BMPRII, which consist a negative feedback loop that balances BMP signaling and maintains cell homeostasis in neurons.
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