miR-199a-3p inhibits cell proliferation and induces apoptosis by targeting YAP1, suppressing Jagged1-Notch signaling in human hepatocellular carcinoma

Journal of Biomedical Science

Research

Kewei Ren¹  Zhen Li¹  Wenzhe Zhang¹  Tengfei Li¹  Gang Wu¹  Jianzhuang Ren¹ 

[1] Department of Radiology, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, 450052, Zhengzhou, Henan, People’s Republic of China;Interventional Institute of Zhengzhou University, 450052, Zhengzhou, People’s Republic of China;Interventional Treatment and Clinical Research Center of Henan Province, 450052, Zhengzhou, People’s Republic of China;

关键词: Hepatocellular carcinoma;    miR-199a-3p;    Yes associated protein 1;    Jagged1;    Notch signaling;   

DOI  :  10.1186/s12929-016-0295-7

 received in 2016-08-04, accepted in 2016-11-03,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundmiR-199a-3p was significantly downregulated in the majority of human hepatocellular carcinoma (HCC) tissues and HCC cell lines. Yes associated protein 1 (YAP1) was overexpressed in human HCC, which promoted HCC development and progression by upregulating Jagged1 and activating the Notch pathway. We searched potential targets of miR-199a-3p with DIANA, TargetScan and PicTar tools, and found that YAP1 is one of the potential targets. Based on these findings, we speculated that miR-199a-3p might suppress HCC growth by targeting YAP1, downregulating Jagged1 and suppressing the Notch pathway.ResultsWe determined the expression of miR-199a-3p and YAP1 by quantitative Real-Time PCR (qRT-PCR) and western blot assays, respectively, and found downregulation of miR-199a-3p and upregulation of YAP1 in HCC cell lines. Cell proliferation and apoptosis assays showed that miR-199a-3p suppresses HCC cell proliferation and promotes apoptosis, and knockdown of YAP1 has similar role. Furthermore, we verified that miR-199a-3p can directly target YAP1. We further investigated and confirmed that miR-199a-3p and YAP1 regulate HCC cell proliferation and apoptosis through Jagged1-Notch signaling.ConclusionmiR-199a-3p targets YAP1, downregulates Jagged1 and suppresses the Notch signaling to inhibit HCC cell proliferation and promote apoptosis. These findings provide new insights into the mechanism by which miR-199a-3p suppresses HCC cell proliferation and induces apoptosis.

【 授权许可】

CC BY   
© The Author(s). 2016