Open AccessUpregulated miR‐1258 regulates cell cycle and inhibits cell proliferation by directly targeting E2F8 in CRC
Author(s) -
Zhang Zhiyuan,
Li Jie,
Huang Yuanjian,
Peng Wen,
Qian Wenwei,
Gu Jiou,
Wang Qingyuan,
Hu Tao,
Ji Dongjian,
Ji Bing,
Zhang Yue,
Wang Shijia,
Sun Yueming
Publication year - 2018
Publication title -
cell proliferation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.647
H-Index - 74
eISSN - 1365-2184
pISSN - 0960-7722
DOI - 10.1111/cpr.12505
Subject(s) - cell cycle , cell growth , downregulation and upregulation , biology , cyclin d1 , cancer research , microrna , western blot , cell cycle checkpoint , microbiology and biotechnology , cell , gene , genetics
Objectives Micro RNA s (mi RNA s) as small noncoding RNA molecules function by regulating their target genes negatively. MiR‐1258 was widely researched in multicancers, but its role remains unclear in colorectal cancer ( CRC ). Methods The expression of miR‐1258 and its specific target gene were detected in human CRC specimens and cell lines by mi RNA RT ‐ PCR , qRT ‐ PCR and Western blot. The effects of miR‐1258 on CRC proliferation were evaluated using CCK ‐8 assays, EdU incorporation, colony formation assays and cell‐cycle assays; in vitro and the in vivo effects were investigated using a mouse tumorigenicity model. Luciferase reporter and RIP assays were employed to identify interactions between miR‐1258 and its specific target gene. Results MiR‐1258 was downregulated in CRC tissues and CRC cell lines, and upregulated miR‐1258 was proved to inhibit proliferation and arrest cell cycle at G0/G1 in vitro and vivo. Luciferase reporter, RIP and western blot assays revealed E2F8 to be a direct target of miR‐1258. The effects of miR‐1258 in proliferation and cell cycle regulation can be abolished by E2F8 through rescue experiments. By directly targeting E2F8, miR‐1258 influenced the expression of several cell‐cycle factors, including cyclin D1 ( CCND 1) and cyclin dependent kinase inhibitor 1A (p21). Conclusion MiR‐1258 may function as a suppressive factor by negatively controlling E2F8, thus, highlighting the potential role of miR‐1258 as a therapeutic target for human CRC .