MyoD is regulated by the miR-29a-Tet1 pathway in C2C12 myoblast cells
MyoD is regulated by the miR-29a-Tet1 pathway in C2C12 myoblast cells
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DOI：
10.2334/josnusd.15-0684
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发表时间：
2016-06-01
影响因子：
1.9
通讯作者：
Gomi, Kazuhiro
中科院分区：
文献类型：
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作者：
Chikenji, Akiyoshi;Ando, Hitoshi;Gomi, Kazuhiro
骨骼肌的发生是由相当数量的microRNAs （miRNAs）调控的。miRNA调控网络是复杂的，它们如何运作的细节尚不清楚。在本研究中，MTT检测证实miR-29a是最有效的miR-29平行体。微阵列分析显示，在C2C12小鼠成肌细胞中，miR-29a抑制导致10 - 11易位酶-1 (Tel1) mRNA上调。我们使用实时RT-PCR研究了miR-29a-Tel1信号通路下游的作用因素。Tell抑制上调MyoD表达，miR-29a抑制下调MyoD表达，而细胞周期蛋白依赖性激酶6 （Cdk6）的表达则以相反的方式调节。这些结果表明，miR-29a-Tet1通路上调MyoD表达，反过来下调Cdk6表达。然而，其他肌生成因子如血清反应因子（Srf）、肌细胞增强因子2家族（Mef2a、b和c）、肌生成素、肌生成调节因子4 （Mrf4）、肌酸激酶（Mck）和其他细胞周期调节因子如Cdk4和胸腺嘧啶DNA糖基酶（Tdg）的表达变化不能仅用miR-29a-Tet1途径来解释。miR29a-Tet1通路可能是C2C12细胞复杂的肌生成调节网络的一部分。
Skeletal myogenesis is regulated by a considerable number of microRNAs (miRNAs). miRNA regulatory networks are complicated, and details of how they operate remain unclear. In this study, MTT assays confirmed that miR-29a is the most effective miR-29 paralog. Microarray analysis demonstrated upregulation of ten-eleven translocation enzyme-1 (Tel1) mRNA in response to miR-29a inhibition in C2C12 murine myoblast cells. We investigated the factors acting downstream in the miR-29a-Tel1 signal pathway using real-time RT-PCR. MyoD expression was upregulated by Tell inhibition and downregulated by miR-29a inhibition, whereas expression of cyclin-dependent kinase 6 (Cdk6) was regulated in an opposite manner. These results suggest that the miR-29a-Tet1 pathway upregulates MyoD expression and conversely down regulates Cdk6 expression. However, changes in the expression of other myogenic factors such as serum response factor (Srf), the myocyte enhancer factor 2 family (Mef2a, b and c), myogenin, myogenic regulatory factor 4 (Mrf4), muscle creatine kinase (Mck), and other cell cycle regulators such as Cdk4 and thymine DNA glycosylase (Tdg) cannot be explained in terms of the miR-29a-Tet1 pathway alone. The miR29a-Tet1 pathway may be part of a complex myogenic regulatory network in C2C12 cells.