Key Laboratory of Chicken Genetics and Breeding, Ministry of Agriculture, Harbin, 150030, Heilongjiang, China.
Key Laboratory of Animal Genetics, Breeding and Reproduction, Education Department of Heilongjiang Province, Harbin, 150030, Heilongjiang, China.
Sci Rep. 2017 Nov 20;7(1):15852. doi: 10.1038/s41598-017-15626-9.
The miR-17-92 cluster has been well studied in mammals but less extensively studied in birds. Here, we demonstrated that miR-17-92 cluster overexpression promoted the proliferation of DF1 cells and immortalized chicken preadipocytes (ICPA-1), and miR-17-5p and miR-20a, members of the miR-17-92 cluster, targeted MAP3K2. Further analysis showed that MAP3K2 overexpression reduced the proliferation of DF1 and ICPA-1 cells and attenuated the promotive effect of the miR-17-92 cluster on cell proliferation. Downstream gene expression analysis of the MAPK signalling pathway showed that MAP3K2 overexpression decreased c-Myc expression; in contrast, MAP3K2 knockdown using RNA interference and miR-17-92 cluster overexpression increased c-Myc expression. Furthermore, c-Myc overexpression promoted miR-17-92 cluster expression and DF1 cell proliferation. Taken together, these data indicated that miR-17-92 promotes chicken cell proliferation at least in part by the upregulation of c-Myc via targeting MAP3K2, and the miR-17-92 cluster, c-Myc and E2F1 form a complex regulatory network in chicken cell proliferation.
miR-17-92 簇在哺乳动物中研究较多，但在鸟类中研究较少。在这里，我们证明 miR-17-92 簇的过表达促进了 DF1 细胞和鸡前体脂肪细胞（ICPA-1）的增殖，miR-17-5p 和 miR-20a 是 miR-17-92 簇的成员，靶向 MAP3K2。进一步分析表明，MAP3K2 的过表达减少了 DF1 和 ICPA-1 细胞的增殖，并减弱了 miR-17-92 簇对细胞增殖的促进作用。MAPK 信号通路的下游基因表达分析表明，MAP3K2 的过表达降低了 c-Myc 的表达；相反，使用 RNA 干扰使 MAP3K2 敲低和 miR-17-92 簇过表达增加了 c-Myc 的表达。此外，c-Myc 的过表达促进了 miR-17-92 簇的表达和 DF1 细胞的增殖。总之，这些数据表明，miR-17-92 通过靶向 MAP3K2 上调 c-Myc 至少部分促进了鸡细胞的增殖，miR-17-92 簇、c-Myc 和 E2F1 在鸡细胞增殖中形成了一个复杂的调控网络。
