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miR-377-3p 通过调控 LIFR 来调节人骨髓间充质干细胞的成脂分化。

miR-377-3p regulates adipogenic differentiation of human bone marrow mesenchymal stem cells by regulating LIFR.

机构信息

Key Laboratory of System Bio-medicine of Jiangxi Province, Jiujiang University, Jiujiang, Jiangxi, People's Republic of China.

Clinical Skills Center, Affiliated Hospital of Jiujiang University, Jiujiang, Jiangxi, People's Republic of China.

出版信息

Mol Cell Biochem. 2018 Dec;449(1-2):295-303. doi: 10.1007/s11010-018-3366-0. Epub 2018 Jun 29.

DOI:10.1007/s11010-018-3366-0
PMID:29959592
Abstract

MicroRNAs are members of the family of non-coding small RNAs that regulate gene expression either by inhibiting mRNA translation or by promoting mRNA degradation at the post-transcriptional level. They play an important role in the differentiation of human bone marrow mesenchymal stem cells (hMSCs) into adipocytes. However, the role of microRNAs in this process remains to be poorly understood. Here, we observed that miR-377-3p expression was markedly decreased during adipogenic differentiation of hMSCs. Overexpression of miR-377-3p decreased adipocyte differentiation and downregulated the expression of adipogenic markers. Meanwhile, bioinformatics-based studies suggested that LIFR is a target of miR-377-3p. Further analysis confirmed that expression of LIFR present markedly increased during adipogenic differentiation of hMSCs. In addition, downregulation expression of LIFR significantly inhibited the process of adipocyte differentiation. To confirm the relation between miR-377-3p and LIFR, luciferase reporter assays were carried out. The results indicated that miR-377-3p bound directly to the 3'-untranslated region of LIFR. These data indicate that miR-377-3p suppressed adipogenesis of hMSCs by targeting LIFR, which provides novel insights into the molecular mechanism of miRNA-mediated cellular differentiation.

摘要

微小 RNA 是一类非编码小 RNA 家族成员,通过抑制 mRNA 翻译或在转录后水平促进 mRNA 降解来调节基因表达。它们在人类骨髓间充质干细胞(hMSCs)向脂肪细胞分化中发挥重要作用。然而,微小 RNA 在这个过程中的作用仍知之甚少。在这里,我们观察到 miR-377-3p 在 hMSCs 的成脂分化过程中表达明显下调。miR-377-3p 的过表达降低了脂肪细胞分化,并下调了脂肪生成标志物的表达。同时,基于生物信息学的研究表明 LIFR 是 miR-377-3p 的靶标。进一步的分析证实,LIFR 在 hMSCs 的成脂分化过程中表达明显增加。此外,下调 LIFR 的表达显著抑制了脂肪细胞分化的过程。为了确认 miR-377-3p 和 LIFR 之间的关系,进行了荧光素酶报告基因检测。结果表明,miR-377-3p 直接结合到 LIFR 的 3'-非翻译区。这些数据表明,miR-377-3p 通过靶向 LIFR 抑制 hMSCs 的脂肪生成,为 miRNA 介导的细胞分化的分子机制提供了新的见解。

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