Clusterin contributes to hepatitis C virus-related hepatocellular carcinoma by regulating autophagy

• Published in: Life sciences (1973) Vol. 256; p. 117911
• Main Authors: Fu, Na, Du, Huijuan, Li, Dongdong, Lu, Yu, Li, Wencong, Wang, Yang, Kong, Lingbo, Du, Jinghua, Zhao, Suxian, Ren, Weiguang, Han, Fang, Wang, Rongqi, Zhang, Yuguo, Nan, Yuemin
• Format: Journal Article
• Language: English
• Published: New York Elsevier Inc 01.09.2020; Elsevier BV
• Subjects: Autophagy; Biotechnology; Clusterin; Core protein; Gene expression; Genes; Hepatitis; Hepatitis C; Hepatitis C virus; Hepatocellular carcinoma; hepatoma; Immunohistochemistry; Liver cancer; mammals; Phagocytosis; plasmids; protein synthesis; Proteins; Rapamycin; Regulatory mechanisms (biology); siRNA; therapeutics; TOR protein; Western blotting; Hepatocellular carcinoma; Hepatitis C virus; Autophagy; Clusterin
• ISSN: 0024-3205; 1879-0631; 1879-0631
• DOI: 10.1016/j.lfs.2020.117911

To explore the potential regulatory mechanism of differentially expressed mRNAs in Hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC). Patients with HCV-related HCC and age- and gender-matched healthy subjects were enrolled. Differentially expressed mRNAs in the plasma were detected by digital gene expression (DGE) profile analysis. HepG2 and SMMC7721 cells stably transfected with HCV-core protein and the control plasmid were established. And small interfering RNA (siRNA) was used to knockdown the target gene in HCV core-expressing HCC cell lines. mRNA expression was determined by qRT-PCR. Protein expression was measured by Western blot and immunohistochemistry staining. DGE profile data showed aberrant mRNA expression contributed to the progression of HCV-HCC, and clusterin (CLU), which was significantly highly expressed, was chosen as a candidate gene. Further evidence showed CLU was highly expressed in tumor tissues of HCV-HCC patients and HCV core-expressing HCC cell lines, accompanied with enhanced autophagy and upregulation of pro-autophagy genes. And knockdown of CLU in HCC cell lines suppressed cell autophagy, which was indicated by decreased expression of autophagy marker light chain 3B (LC3B) ІІ/І ratio, and downregulated pro-autophagy genes like Beclin1, autophagy-related protein 7 (Atg7) and Lamp2. On the other hand, anti-autophagy genes or regulators, including p62 and phosphorylated mammalian target of rapamycin (p-mTOR), were notably upregulated. CLU could promote the progression of HCV-related HCC by regulating autophagy, which might be a potential therapeutic target of HCV-HCC.