circFGFR4 Promotes Differentiation of Myoblasts via Binding miR-107 to Relieve Its Inhibition of Wnt3a.
circFGFR4 Promotes Differentiation of Myoblasts via Binding miR-107 to Relieve Its Inhibition of Wnt3a.
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circFGFR4通过结合miR-107解除其对Wnt3a的抑制促进成肌细胞分化
DOI：
10.1016/j.omtn.2018.02.012
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发表时间：
2018-06-01
期刊：
影响因子：
--
通讯作者：
Chen H
中科院分区：
文献类型：
--
作者：
Li H;Wei X;Yang J;Dong D;Hao D;Huang Y;Lan X;Plath M;Lei C;Ma Y;Lin F;Bai Y;Chen H
肌肉发育受一系列复杂过程的调控，而非编码RNA，如microRNAs(MiRNAs)和CircRNAs(CircRNAs)，已被报道在调控成肌细胞的增殖和分化中发挥重要作用。我们发现miR-107在秦川牛的骨骼肌中高表达。过表达miR-107抑制了牛成肌细胞的分化，保护了细胞的凋亡。通过荧光素酶活性、实时荧光定量聚合酶链式反应和Western blotting鉴定Wnt3a为miR-107的靶标。Wnt3a基因的敲除抑制了牛成肌细胞的分化和凋亡，其作用类似于miR-107过表达。我们还发现CircFGFR4可以促进成肌细胞分化和诱导细胞凋亡。通过荧光素酶筛选和RNA下拉实验，观察到大约有FGFR4与miR-107结合。过表达CircFGFR4可增加WNT3a的表达，而这种作用可被miR-107取消。这些结果表明，CircFGFR4结合的miR-107通过靶向Wnt3a促进了牛原代成肌细胞的分化。
Muscle development is regulated under a series of complicate processes, and non-coding RNAs, such as microRNAs (miRNAs) and circular RNAs (circRNAs), have been reported to play important roles in regulating myoblast proliferation and differentiation. We found that miR-107 expression was high in skeletal muscle of Qinchuan cattle. Overexpression of miR-107 inhibited bovine myoblasts differentiation and protected cells from apoptosis. Wnt3a was identified as a target of miR-107 by luciferase activity, real-time qPCR, and western blotting assays. Knockdown of Wnt3a inhibited bovine myoblasts differentiation and apoptosis, and this effect was similar to miR-107 overexpression. We also found circFGFR4 to promote myoblasts differentiation and to induce cell apoptosis. Via luciferase screening and RNA pull-down assays, circFGFR4 was observed to sponge miR-107. Overexpression of circFGFR4 increased the expression of Wnt3a, whereas this effect was abolished by miR-107. These results demonstrated that circFGFR4 binding miR-107 promotes cell differentiation via targeting Wnt3a in bovine primary myoblasts.
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