MicroRNA-30a suppresses autophagy-mediated anoikis resistance and metastasis in hepatocellular carcinoma

• Published in: Cancer letters Vol. 412; pp. 108 - 117
• Main Authors: Fu, Xiu-Tao, Shi, Ying-Hong, Zhou, Jian, Peng, Yuan-Fei, Liu, Wei-Ren, Shi, Guo-Ming, Gao, Qiang, Wang, Xiao-Ying, Song, Kang, Fan, Jia, Ding, Zhen-Bin
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 01.01.2018; Elsevier Limited
• Subjects: Adult; Aged; Animals; Anoikis; Apoptosis; Autophagy; Autophagy - physiology; Autophagy-Related Protein 5 - physiology; Cancer; Carcinoma, Hepatocellular - pathology; Cell growth; Cell Line, Tumor; Female; Hepatocellular carcinoma; Hepatology; Humans; Kinases; Liver cancer; Liver Neoplasms - pathology; Lung cancer; Lung Neoplasms - secondary; Male; Metastases; Metastasis; Mice; Mice, Inbred BALB C; MicroRNAs - physiology; Middle Aged; miRNA; MiroRNA-30a; Neoplasm Metastasis; Neoplasm Recurrence, Local; Phagocytosis; Ribonucleic acid; RNA; Rodents; Tumors; miR-30a; MiroRNA-30a; miRNAs; Hepatocellular carcinoma; HCC; Metastasis; Autophagy; GFP; DMEM; FBS; Anoikis; SEM; EBSS; EthD-1
• ISSN: 0304-3835; 1872-7980; 1872-7980
• DOI: 10.1016/j.canlet.2017.10.012

MiRNA-30a (miR-30a) was previously reported as one of metastatic hepatocellular carcinoma (HCC)-related microRNAs. However, the function of miR-30a on enhancing our biological understanding of HCC metastasis is not clear. This study demonstrated that miR-30a was significantly down-regulated in HCC tissues and cell lines, and was associated with vascular invasion, metastasis potential and recurrent disease in HCC. Functional studies confirmed that miR-30a could inhibit the metastasis of HCC in a well-established nude mouse model of lung metastasis. Moreover, miR-30a was proved to prevent anoikis inhibition of HCC cells in vivo and in vitro. Mechanically, autophagy related protein Beclin 1 and Atg5 were direct downstream targets of miR-30a, and mediated autophagy activity influence of miR-30a in HCC. Taken together, downregulated miR-30a in metastatic HCC mediates Beclin 1 and Atg5-dependent autophagy, which confers anoikis resistance in HCC cells. The molecular basis of autophagy action during this process partly contributes to the HCC metastasis, suggesting that targeting autophagy via miR-30a may have therapeutic implications for the prevention of HCC recurrence/metastasis. •miR-30a expression is correlated with metastasis in HCC.•miR-30a inhibits the metastasis of HCC in vivo.•miR-30a prevents anoikis inhibition of HCC cells in vivo and in vitro.•Downregulated miR-30a in metastatic HCC mediates Beclin 1 and Atg5-dependent autophagy.