miR-377-3p regulates adipogenic differentiation of human bone marrow mesenchymal stem cells by regulating LIFR
miR-377-3p regulates adipogenic differentiation of human bone marrow mesenchymal stem cells by regulating LIFR
复制标题
miR-377-3p通过调节LIFR调控人骨髓间充质干细胞的成脂分化
DOI：
10.1007/s11010-018-3366-0
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发表时间：
2018-12-01
影响因子：
4.3
通讯作者：
Wang, Tao
中科院分区：
文献类型：
--
作者：
Li, Xingnuan;Yang, Yaofang;Wang, Tao
microrna是非编码小rna家族的成员，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。它们在人骨髓间充质干细胞（hMSCs）向脂肪细胞的分化过程中发挥重要作用。然而，microrna在这一过程中的作用仍然知之甚少。在这里，我们观察到miR-377-3p的表达在hMSCs的成脂分化过程中显著降低。过表达miR-377-3p可抑制脂肪细胞分化，下调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的靶点。进一步分析证实，在hMSCs的成脂分化过程中，LIFR的表达明显增加。此外，下调LIFR表达可显著抑制脂肪细胞分化过程。为了确认miR-377-3p与LIFR之间的关系，我们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，这为mirna介导的细胞分化的分子机制提供了新的见解。
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.