MicroRNA-370 functions as a tumor suppressor in hepatocellular carcinoma via inhibition of the MAPK/JNK signaling pathway by targeting BEX2

• Published in: Journal of human genetics Vol. 64; no. 12; pp. 1203 - 1217
• Main Authors: Wang, Xin, Zhu, Wenyan, Xu, Chuanshen, Wang, Feng, Zhu, Xiaodan, Sun, Yandong, Guo, Yuan, Fu, Xiaoyue, Zhang, Yong, Zang, Yunjin
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.12.2019
• Subjects: Antitumor activity; Apoptosis; Apoptosis - genetics; Carcinoma, Hepatocellular - genetics; Cell Line, Tumor; Cell migration; Cell Movement - genetics; Cell proliferation; Cell Proliferation - genetics; Cirrhosis; DNA microarrays; Down-Regulation - genetics; Female; Gene expression; Gene Expression Regulation, Neoplastic - genetics; Genes, Tumor Suppressor - physiology; Hep G2 Cells; Hepatocellular carcinoma; Humans; Kinases; Liver cancer; Liver cirrhosis; Liver diseases; Liver Neoplasms - genetics; Male; Malignancy; MAP kinase; MAP Kinase Signaling System - genetics; MicroRNAs; MicroRNAs - genetics; Middle Aged; miRNA; Neoplasm Invasiveness - genetics; Nerve Tissue Proteins - genetics; Signal transduction; Signal Transduction - genetics; Tumor suppressor genes
• ISSN: 1434-5161; 1435-232X; 1435-232X
• DOI: 10.1038/s10038-019-0653-x

Hepatocellular carcinoma (HCC) is a primary malignancy of the liver and occurs predominantly in patients with underlying chronic liver disease and cirrhosis. Accumulating studies have revealed that microRNAs (miRNAs) play a critical role in the development and progression of HCC. Through microarray-based gene expression profiling of HCC, miR-370, and BEX2 were identified in HCC. Hence, this study aimed to evaluate their abilities on the cellular processes in HCC. It was determined that BEX2 was highly expressed and miR-370 was poorly expressed in HCC cell lines and tissues. Then, the cell line presenting with the highest BEX2 expression and the lowest miR-370 expression was selected for subsequent gain- and loss-of-function experimentation. The antitumor effect of miR-370 on HCC cell proliferation, invasion, migration, and apoptosis, as well as the MAPK/JNK signaling pathway was examined. Meanwhile, the interaction among miR-370, BEX2, and MAPK/JNK signaling pathway was identified. BEX2 is verified to be a target of miR-370. Moreover, miR-370 exerted antitumor effect on HCC development through suppression of the MAPK/JNK signaling pathway by targeting BEX2. Later, it was further verified by in vivo experiment that overexpression of miR-370 inhibited tumor growth. Above results provide evidence that miR-370 could downregulate BEX2 gene and inhibit activation of MAPK/JNK signaling pathway, thus inhibiting the development of HCC. It provides a worth-trying novel therapeutic target for HCC treatment.