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
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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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Available from: G. Ian Gallicano, Oct 10, 2015
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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.
    Gene 05/2015; 569(2). DOI:10.1016/j.gene.2015.05.060 · 2.14 Impact Factor
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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.
    PLoS ONE 12/2013; 8(12):e83067. DOI:10.1371/journal.pone.0083067 · 3.23 Impact Factor
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    • "Several members of the miR-17 family, including miR-17-5p, miR-20a, miR-106a and miR-93, have previously been found to be expressed during early mammalian development and regulate stem cell differentiation [13]. In addition, the miR-17-92 cluster was demonstrated to accelerate adipocyte differentiation by negatively regulating tumor-suppressor Rb2/p130 [14]. "
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    ABSTRACT: microRNAs (miRNAs) have been reported to play an essential role in the regulation of brown adipocyte adipogenesis. In the present study, we investigated the role of the miR-106b-93 cluster in the differentiation of brown adipocytes. We found that knockdown of miR-106b and miR-93 significantly induced the expression of brown fat-specific genes and promoted the accumulation of lipid-droplet in differentiating brown adipocytes. In addition, ectopic expression of miR-106b and miR-93 suppressed the mRNA level of Ucp1, a selective hallmark of brown adipocytes. Furthermore, the expression levels of miR-106b and miR-93 are higher in brown adipose tissues of high fat diet-induced obese mice compared to control mice. Taken together, our results identify miR-106b and miR-93 as negative regulators of brown adipocyte differentiation and the miR-106b-93 cluster may play an important role in regulating energy homeostasis.
    Biochemical and Biophysical Research Communications 08/2013; 438(4). DOI:10.1016/j.bbrc.2013.08.016 · 2.30 Impact Factor
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