E2F1-miR-20a-5p/20b-5p auto-regulatory feedback loop involved in myoblast proliferation and differentiation.
E2F1-miR-20a-5p/20b-5p auto-regulatory feedback loop involved in myoblast proliferation and differentiation.
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DOI：
10.1038/srep27904
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发表时间：
2016-06-10
影响因子：
4.6
通讯作者：
Zhang X
中科院分区：
文献类型：
--
作者：
Luo W;Li G;Yi Z;Nie Q;Zhang X
miR-17家族microRNA（miRNAs）对胚胎发育至关重要，然而，它们在肌肉发育中的作用仍不清楚。miR-20 a-5 p和miR-20 b-5 p属于miR-17家族，分别转录自miR-17~92和miR-106 a ~363簇。本研究发现miR-20 a-5 p和miR-20 b-5 p通过直接结合E2 F转录因子1（E2 F1）mRNA的3′ UTR，促进成肌细胞分化，抑制成肌细胞增殖。E2 F1是生物体正常发育的重要转录因子。E2 F1在成肌细胞中的过表达促进成肌细胞增殖，抑制成肌细胞分化。相反，E2 F1抑制诱导成肌细胞分化和抑制成肌细胞增殖。此外，E2 F1可直接与miR-17~92和miR-106 a ~363簇的启动子结合并激活其转录，且E2 F1蛋白表达与成肌细胞分化过程中pri-miR-17~92和pri-miR-106 a ~363的表达相关。这些结果提示E2 F1与miR-20 a-5 p/20 b-5 p之间存在自调节反馈环，提示miR-20 a-5 p、miR-20 b-5 p和E2 F1通过E2 F1与miR-20 a-5 p/20 b-5 p之间的自调节参与成肌细胞的增殖和分化。这些发现为肌肉分化机制提供了新的见解，并进一步阐明了肌肉发育和肌肉疾病的理解。
miR-17 family microRNAs (miRNAs) are crucial for embryo development, however, their role in muscle development is still unclear. miR-20a-5p and miR-20b-5p belong to the miR-17 family and are transcribed from the miR-17~92 and miR-106a~363 clusters respectively. In this study, we found that miR-20a-5p and miR-20b-5p promoted myoblast differentiation and repressed myoblast proliferation by directly binding the 3′ UTR of E2F transcription factor 1 (E2F1) mRNA. E2F1 is an important transcriptional factor for organism’s normal development. Overexpression of E2F1 in myoblasts promoted myoblast proliferation and inhibited myoblast differentiation. Conversely, E2F1 inhibition induced myoblast differentiation and repressed myoblast proliferation. Moreover, E2F1 can bind directly to promoters of the miR-17~92 and miR-106a~363 clusters and activate their transcription, and E2F1 protein expression is correlated with the expression of pri-miR-17~92 and pri-miR-106a~363 during myoblast differentiation. These results suggested an auto-regulatory feedback loop between E2F1 and miR-20a-5p/20b-5p, and indicated that miR-20a-5p, miR-20b-5p and E2F1 are involved in myoblast proliferation and differentiation through the auto-regulation between E2F1 and miR-20a-5p/20b-5p. These findings provide new insight into the mechanism of muscle differentiation, and further shed light on the understanding of muscle development and muscle diseases.