MicroRNA-214-3p targets the PLAGL2-MYH9 axis to suppress tumor proliferation and metastasis in human colorectal cancer

Zili Zhou(Union Hospital), Liang Wu(Huazhong University of Science and Technology), Zhengyi Liu(Zhengzhou University), Xudan Zhang(Union Hospital), Shengbo Han(Huazhong University of Science and Technology), Ning Zhao(Union Hospital), Haijun Bao(Huazhong University of Science and Technology), Wenzheng Yuan(Renmin Hospital of Wuhan University), Jinhuang Chen(Union Hospital), Jintong Ji(Central Hospital of Wuhan), Xiaogang Shu(Huazhong University of Science and Technology)
Aging
May 15, 2020
Cited by 86Open Access
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Abstract

Evidence has shown that microRNAs (miRNAs) participate in the progression of CRC. Previous studies have indicated that miR-214-3p is abnormally expressed in various malignant tumors. However, the biological function it plays in CRC and the potential mechanism are unclear. Here, we demonstrated that miR-214-3p was obviously downregulated in CRC. Moreover, we found a strong correlation between the miR-214-3p level and tumor size and lymphatic metastasis. Furthermore, when miR-214-3p was decreased by an Lv-miR-214-3p inhibitor, the proliferation and migration of SW480 and HCT116 cells were significantly increased. As expected, the ability of proliferation and migration was significantly suppressed when miR-214-3p was overexpressed in DLD1 cells. According to the dual-luciferase reporter results, PLAGL2 was found to be a direct downstream molecule of miR-214-3p. Chromatin immunoprecipitation (CHIP) confirmed that MYH9, a well-known cytoskeleton molecule in CRC, was a direct targeting gene of PLAGL2. Silencing PLAGL2 or MYH9 could reverse the effect of a miR-214-3p inhibitor on CRC cells. In summary, our studies proved that low expression of miR-214-3p and overexpression of downstream PLAGL2 in CRC indicated a poor prognosis. MiR-214-3p suppressed the malignant behaviors of colorectal cancer by regulating the PLAGL2/MYH9 axis. MiR-214-3p might be a novel therapeutic target or prognostic marker for CRC.


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