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

Autor: Yuguo Zhang, Dongdong Li, Wencong Li, Ling-bo Kong, Na Fu, Huijuan Du, Jinghua Du, Suxian Zhao, Yuemin Nan, Yang Wang, Fang Han, Rongqi Wang, Wei-guang Ren, Yu Lu
Rok vydání: 2020
Předmět:
0301 basic medicine
Male
Small interfering RNA
Carcinoma
Hepatocellular
Cell
Apoptosis
Hepacivirus
030226 pharmacology & pharmacy
Autophagy-Related Protein 7
General Biochemistry
Genetics and Molecular Biology
03 medical and health sciences
0302 clinical medicine
Downregulation and upregulation
Cell Line
Tumor
Lysosomal-Associated Membrane Protein 2
Gene expression
medicine
Autophagy
Humans
RNA
Messenger
General Pharmacology
Toxicology and Pharmaceutics
Phosphorylation
RNA
Small Interfering
Aged
Gene knockdown
Genomic Library
LAMP2
Clusterin
biology
TOR Serine-Threonine Kinases
Liver Neoplasms
RNA-Binding Proteins
General Medicine
Middle Aged
digestive system diseases
Gene Expression Regulation
Neoplastic
030104 developmental biology
medicine.anatomical_structure
Liver
Gene Knockdown Techniques
biology.protein
Cancer research
Beclin-1
Female
Signal Transduction
Zdroj: Life sciences. 256
ISSN: 1879-0631
Popis: Aims To explore the potential regulatory mechanism of differentially expressed mRNAs in Hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC). Main methods 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. Key findings 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. Significance CLU could promote the progression of HCV-related HCC by regulating autophagy, which might be a potential therapeutic target of HCV-HCC.
Databáze: OpenAIRE
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