Kang Tingting, Xing Wenkai, Xi Yu, Chen Kun, Zhan Mengsi, Tang Xiaoyin, Wang Yueying, Zhang Ruirui, Lei Minggang
Key Laboratory of Swine Genetics and Breeding of Agricultural Ministry, and Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, China.
J Cell Biochem. 2020 Dec;121(12):4827-4837. doi: 10.1002/jcb.29710. Epub 2020 Apr 29.
MicroRNA-543 (miR-543) has been found to play a suppressive role in various human cancers in many studies, whereas the specific functions of miR-543 in muscle development remain poorly understood. Here, we found that the expression of miR-543 was high in skeletal muscle and increased during the differentiation of C2C12 cells. Overexpression of miR-543 repressed C2C12 cell proliferation and promoted differentiation, while knockdown of miR-543 expression produced the opposite results. During myogenesis, we predicted and verified that Krüppel-like factor 6 (KLF6), a suppressor of multiple tumor cells, was a target gene of miR-543. Then, miR-543 was found to specifically target KLF6 and repress its expression. Besides this, knockdown of KLF6 promoted the differentiation but inhibited the proliferation of C2C12 cells. Si-KLF6 can rescue the influence of miR-543 inhibitor on C2C12 cell differentiation. Our results indicate a new regulatory mechanism of miR-543 on KLF6 expression and suggest the possibility of using the miR-543/KLF6 pathway as a potential target for studying myogenesis.
在许多研究中发现,微小RNA-543(miR-543)在多种人类癌症中发挥抑制作用,而miR-543在肌肉发育中的具体功能仍知之甚少。在此,我们发现miR-543在骨骼肌中表达较高,且在C2C12细胞分化过程中升高。miR-543的过表达抑制C2C12细胞增殖并促进分化,而敲低miR-543表达则产生相反的结果。在肌生成过程中,我们预测并验证了多种肿瘤细胞的抑制因子Krüppel样因子6(KLF6)是miR-543的靶基因。然后,发现miR-543特异性靶向KLF6并抑制其表达。除此之外,敲低KLF6可促进C2C12细胞分化但抑制其增殖。Si-KLF6可挽救miR-543抑制剂对C2C12细胞分化的影响。我们的结果表明miR-543对KLF6表达有新的调控机制,并提示将miR-543/KLF6通路作为研究肌生成潜在靶点的可能性。