J Cancer 2020; 11(9):2476-2484. doi:10.7150/jca.37748

Research Paper

MicroRNA-19a-3p regulates cell growth through modulation of the PIK3IP1-AKT pathway in hepatocellular carcinoma

Hai-Xiang Sun1,*, Zhang-Fu Yang2,*, Wei-Guo Tang3,*, Ai-Wu Ke1, Wei-ren Liu2, Yan Li1, Chao Gao4, Bo Hu2, Pei-Yao Fu2, Min-Cheng Yu2, Bo-Wen Gao2, Ying-hong Shi2, Jia Fan1,2,4,✉, Yang Xu2,✉

1. Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai 200032, China
2. Department of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai 200032, China
3. Minhang Hospital, Fudan University; Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai 200032, China
4. Institute of Biomedical Sciences, Fudan University, Shanghai 200032, China
* contributed equally

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Citation:
Sun HX, Yang ZF, Tang WG, Ke AW, Liu Wr, Li Y, Gao C, Hu B, Fu PY, Yu MC, Gao BW, Shi Yh, Fan J, Xu Y. MicroRNA-19a-3p regulates cell growth through modulation of the PIK3IP1-AKT pathway in hepatocellular carcinoma. J Cancer 2020; 11(9):2476-2484. doi:10.7150/jca.37748. Available from http://www.jcancer.org/v11p2476.htm

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Abstract

There are some controversies about the involvement of microRNA (miR)-19a-3p in hepatocellular carcinoma (HCC) biology, even though many studies have shown that it plays an important role in cancer. In this study, we found that miR-19a-3p is usually overexpressed in HCC tissues compared with corresponding peritumorous tissues, and its expression was associated with tumor size and poor overall survival. MiR-19a-3p promoted cell proliferation significantly, and more cells were found in the S phase. In vivo, miR-19a-3p promoted liver tumor growth, and more HCC cells were found in the active cell cycle. Sequencing and bioinformatics analysis predicted that PIK3IP1 is a likely target gene of miR-19a-3p, and we next confirmed it by luciferase and rescue assays. Altogether, our data showed an important role of PIK3IP1 downregulation by miR-19a-3p in HCC progression, and the miR-19a-3p-PIK3IP1-AKT pathway may be a potential therapeutic target.

Keywords: microRNA-19a-3p, miR-19a-3p, phosphatidyl inositol 3-kinase interacting protein 1, PIK3IP1, hepatocellular carcinoma, cell growth