Hepatitis B virus promotes cancer cell migration by downregulating miR-340-5p expression to induce STAT3 overexpression

• Published in: Cell & bioscience Vol. 7; no. 1; p. 16
• Main Authors: Xiong, Qiushuang, Wu, Shaoshuai, Wang, Jingwen, Zeng, Xianhuang, Chen, Jianwen, Wei, Mingcong, Guan, Haotong, Fan, Chengpeng, Chen, Lang, Guo, Deyin, Sun, Guihong
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 12.04.2017; BioMed Central; BMC
• Subjects: Apoptosis; Breast cancer; Cell adhesion & migration; Cell migration; Cytokines; E-cadherin; Expression vectors; Gene expression; Genes; Genetic aspects; HBV–HCC; Hepatitis; Hepatitis B; Hepatitis B virus; Hepatocellular carcinoma; Hepatocytes; Kinases; Liver cancer; Lymphocytes B; Mesenchyme; Metastasis; MicroRNAs; miR-340-5p; Pathogenesis; Polymerase chain reaction; Proteins; Quantitative analysis; STAT3; Stat3 protein; Transcription; Transfection; Tumorigenesis; Tumors; Vimentin; Western blotting; Wound healing; miR-340-5p; HBV–HCC; Cell migration; STAT3
• ISSN: 2045-3701; 2045-3701
• DOI: 10.1186/s13578-017-0144-8

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide, and infection with hepatitis B virus (HBV) is a leading cause of HCC. Previous studies have demonstrated that expression of the tumor inhibitor miR-340 is significantly downregulated in HCC tissues compared with normal liver tissues. However, the precise biological role of miR-340-5p in HBV-HCC and its molecular mechanism of action remain unknown. Expression of miR-340-5p was downregulated in HBV-associated HCC liver tissue and HBV-infected cells, facilitating migration of liver cancer cells. Signal transducer and activator of transcription (STAT)3 was found to be a direct functional target of miR-340-5p. The regulation of STAT3 expression by miR-340-5p was assessed using qRT-PCR and western blotting, and the effects of exogenous miR-340-5p and STAT3 on the migration of HBV-infected cells were evaluated in vitro using Transwell and wound-healing assays. The expression of E-cadherin and vimentin, associated with epithelial-mesenchymal transition, was also assessed using Western blotting after transfection of miR-340-5p mimics and/or STAT3 expression vectors. Overexpression of STAT3 resulted in rescue of HBV effects, decreased E-cadherin expression, increased vimentin expression, and ultimately, enhanced cell migration. Re-introduction of the STAT3 CDS led to marked reversal of the inhibition of cell migration in HBV-infected cells mediated by miR-340-5p. Hepatitis B virus promotes the migration of liver cancer cells by downregulating miR-340-5p expression to induce STAT3 overexpression. Our results show that STAT3 plays a key role in regulating cell migration in HBV-HCC involving miR-340-5p.