Hepatitis B virus-regulated growth of liver cancer cells occurs through the microRNA-340-5p-activating transcription factor 7-heat shock protein A member 1B axis.

Abstract

Hepatocellular carcinoma (HCC) is a common cancer with poor prognosis. Hepatitis B virus (HBV) is one of the leading causes of HCC, but the precise mechanisms by which this infection promotes cancer development are not fully understood. Recently, miR-340-5p, a microRNA (miRNA) that has been identified as a cancer suppressor gene, was found to inhibit the migration and invasion of liver cancer cells. However, the effect of miR-340-5p on cell proliferation and apoptosis in HBV-associated HCC remains unknown. In our study, we show that miR-340-5p plays an important role during HBV infection and hepatocellular carcinoma development. Specifically, this miRNA directly binds to the mRNA encoding activating transcription factor 7 (ATF7), a protein that both promotes cell proliferation and suppresses apoptosis through its interaction with heat shock protein A member 1B (HSPA1B). We further found that miR-340-5p is downregulated by HBV, which enhances ATF7 expression, leading to enhanced cell proliferation and inhibition of apoptosis. Notably, ATF7 is upregulated in HCC tissue, suggesting that HBV may target miR-340-5p in vivo to promote ATF7/HSPA1B-mediated proliferation and apoptosis and regulate liver cancer progression. This work helps to elucidate the complex interactions between HBV and host miRNAs and further suggests that miR-340-5p may represent a promising candidate for the development of improved therapeutic strategies for HCC.

• Authors: Feifei Song, Mingcong Wei, Jingwen Wang, Yang Liu, Mingxiong Guo, Xiaolu Li, Jun Luo, Junying Zhou, Min Wang, Deyin Guo, Lang Chen, Guihong Sun
• Journal: Cancer science (Cancer Sci) Vol. 110 Issue 5 Pg. 1633-1643 (May 2019) ISSN: 1349-7006 [Electronic] England
• PMID: 30891870 (Publication Type: Journal Article)
• Copyright: © 2019 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Chemical References

• ATF7 protein, human
• Activating Transcription Factors
• HSP70 Heat-Shock Proteins
• HSPA1B protein, human
• MIRN340 microRNA, human
• MicroRNAs

Topics

• Activating Transcription Factors (genetics, metabolism)
• Apoptosis
• Carcinoma, Hepatocellular (genetics, metabolism, virology)
• Cell Line, Tumor
• Cell Proliferation
• Disease Progression
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic
• HSP70 Heat-Shock Proteins (genetics, metabolism)
• Hep G2 Cells
• Hepatitis B (genetics, metabolism)
• Humans
• Liver Neoplasms (genetics, metabolism, virology)
• MicroRNAs (genetics)