miR-99a-5p Regulates the Proliferation and Differentiation of Skeletal Muscle Satellite Cells by Targeting MTMR3 in Chicken
miR-99a-5p Regulates the Proliferation and Differentiation of Skeletal Muscle Satellite Cells by Targeting MTMR3 in Chicken
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DOI：
10.3390/genes11040369
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发表时间：
2020-04-01
期刊：
影响因子：
3.5
通讯作者：
Yin, Huadong
中科院分区：
文献类型：
--
作者：
Cao, Xinao;Tang, Shuyue;Yin, Huadong
非编码RNAs，尤其是microRNAs(MiRNAs)在骨骼肌发育和再生过程中发挥着重要作用。我们之前的测序数据显示miR-99a-5p是鸡胸肌中含量最丰富的miRNAs之一。本研究旨在揭示miR-99a-5p对鸡骨骼肌卫星细胞(SMSCs)增殖和分化的调控机制。通过对细胞增殖活性、细胞周期进程和5-乙炔-29-脱氧尿苷(EDU)活性的研究发现，miR-99a-5P能显著促进SMSCs的增殖。此外，我们还发现miR-99a-5p可以通过降低肌细胞分化标志基因的表达来抑制肌管的形成。通过miR-99a-5p靶基因扫描，我们证实miR-99a-5p直接靶向肌管蛋白相关蛋白3(MTMR3)的3‘非翻译区，并调节其在鸡SMSC增殖和分化过程中的表达水平。我们还研究了MTMR3在肌肉发育中的作用，发现MTMR3的下调显著促进了SMSCs的增殖，但抑制了SMSCs的分化，这与miR-99a-5p的作用相反。总之，我们证明了miR-99a-5p通过靶向MTMR3来调控SMSCs的增殖和分化。
Noncoding RNAs, especially microRNAs (miRNAs), have been reported to play important roles during skeletal muscle development and regeneration. Our previous sequencing data revealed that miR-99a-5p is one of the most abundant miRNAs in chicken breast muscle. The purpose of this study was to reveal the regulatory mechanism of miR-99a-5p in the proliferation and differentiation of chicken skeletal muscle satellite cells (SMSCs). Through the investigation of cell proliferation activity, cell cycle progression, and 5-ethynyl-29-deoxyuridine (EdU) assay, we found that miR-99a-5p can significantly promote the proliferation of SMSCs. Moreover, we found that miR-99a-5p can inhibit myotube formation by decreasing the expression of muscle cell differentiation marker genes. After miR-99a-5p target gene scanning, we confirmed that miR-99a-5p directly targets the 3 ' untranslated region (UTR) of myotubularin-related protein 3 (MTMR3) and regulates its expression level during chicken SMSC proliferation and differentiation. We also explored the role of MTMR3 in muscle development and found that its knockdown significantly facilitates the proliferation but represses the differentiation of SMSCs, which is opposite to the effects of miR-99a-5p. Overall, we demonstrated that miR-99a-5p regulates the proliferation and differentiation of SMSCs by targeting MTMR3.