The functional analysis of transiently upregulated miR-101 suggests a "braking" regulatory mechanism during myogenesis
The functional analysis of transiently upregulated miR-101 suggests a "braking" regulatory mechanism during myogenesis
复制标题
短暂上调的 miR-101 的功能分析表明，肌生成过程中存在“制动”调节机制
DOI：
10.1007/s11427-020-1856-5
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发表时间：
2021-01-27
影响因子：
9.1
通讯作者：
Qu, Lianghu
中科院分区：
文献类型：
--
作者：
Liu, Shurong;Xie, Shujuan;Qu, Lianghu
骨骼肌分化是一个高度协调的过程，涉及许多细胞信号通路和microRNAs（miRNAs）。据报道，一组肌肉特异性miRNA通过抑制细胞生长的关键信号通路来促进肌生成。然而，大多数非肌肉特异性miRNA在分化过程中具有阶段特异性变化的功能作用和调控机制在很大程度上尚不清楚。在这里，我们描述了miR-101 a/B的功能特征，一对非肌肉特异性的miRNA，在C2 C12细胞的肌生成过程中，在一组瞬时上调的miRNA中显示出最大的变化。miR-101 a/B的过表达通过抑制p38/MAPK、干扰素γ和Wnt通路以及增强C/EBP通路来抑制成肌细胞分化。Mef 2a是p38/MAPK通路中的关键蛋白，被认为是miR-101 a/B的直接靶点。有趣的是，我们发现促进肌肉分化的长链非编码RNA（lncRNA）Malat 1与miR-101 a/B相互作用，这种相互作用与Mef 2a mRNA竞争，以缓解肌生成过程中对p38/MAPK通路的抑制。这些结果揭示了瞬时上调的miRNA在分化中的“制动”作用，并为成肌细胞分化和肌发生中的竞争性内源性RNA（ceRNA）调节机制提供了新的见解。
Skeletal muscle differentiation is a highly coordinated process that involves many cellular signaling pathways and microRNAs (miRNAs). A group of muscle-specific miRNAs has been reported to promote myogenesis by suppressing key signaling pathways for cell growth. However, the functional role and regulatory mechanism of most non-muscle-specific miRNAs with stage-specific changes during differentiation are largely unclear. Here, we describe the functional characterization of miR-101a/b, a pair of non-muscle-specific miRNAs that show the largest change among a group of transiently upregulated miRNAs during myogenesis in C2C12 cells. The overexpression of miR-101a/b inhibits myoblast differentiation by suppressing the p38/MAPK, Interferon Gamma, and Wnt pathways and enhancing the C/EBP pathway. Mef2a, a key protein in the p38/MAPK pathway, was identified as a direct target of miR-101a/b. Interestingly, we found that the long non-coding RNA (lncRNA) Malat1, which promotes muscle differentiation, interacts with miR-101a/b, and this interaction competes with Mef2a mRNA to relieve the inhibition of the p38/MAPK pathway during myogenesis. These results uncovered a "braking" role in differentiation of transiently upregulated miRNAs and provided new insights into the competing endogenous RNA (ceRNA) regulatory mechanism in myoblast differentiation and myogenesis.