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The Persistence of Hepatitis C Virus Infection in Hepatocytes Promotes Hepatocellular Carcinoma Progression by Pro-Inflammatory Interluekin-8 Expression

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Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
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Center for Cancer Research, Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
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Program in Tropical Medicine, Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
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Research Center for Cancer Biology, Graduate Institute of Biomedical Science, China Medical University, Taichung 406040, Taiwan
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Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
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Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
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Hepatitis Research Center, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
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Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
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Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung 80756, Taiwan
*
Author to whom correspondence should be addressed.
Academic Editors: Neuman Manuela and Stephen Malnick
Biomedicines 2021, 9(10), 1446; https://doi.org/10.3390/biomedicines9101446
Received: 6 September 2021 / Revised: 23 September 2021 / Accepted: 30 September 2021 / Published: 11 October 2021
Background: A large amount of epidemiological evidence indicates that persistent HCV infection is the main risk factor for HCC. We aimed to study the effects of persistent HCV infection on the interaction of the virus and host cell to identify cancer gene profiles. Methods: Next-generation sequencing (NGS) was used to identify differentially expressed genes between uninfected Huh7.5.1 control cells, short-term HCV (S-HCV), early long-term HCV (eL-HCV), and long-term HCV (L-HCV) infections, which were analyzed using different dynamic bioinformatics and analytic tools. mRNA expression was validated and quantified using q-PCR. One hundred ninety-six serum samples of HCV patients with IFN/RBV treatment were used to study chemokine levels. Results: S-HCV activates an inflammatory response and drives cell death and apoptosis through cell cycle arrest via MAPK signaling. L-HCV promotes cell growth and alters cell adhesion and chemokine signaling via CXCL8-mediated-SRC regulation. A total of 196 serum samples from the HCV and HCV-HCC cohorts demonstrated significantly upregulated pro-inflammatory CXCL8 in non-SVR (persistent HCV infection) patients in the HCV-HCC group. Conclusions: Persistent infection with HCV induced pro-inflammatory CXCL8 and the oncogene SRC, thereby triggering and promoting hepatocarcinogenesis. CXCL8 may be a potential biomarker for monitoring HCV-related HCC progression. View Full-Text
Keywords: hepatitis C virus (HCV); hepatocellular carcinoma (HCC); C-X-C motif ligand 8 (CXCL8); proto-oncogene tyrosine-protein kinase Src (SRC) hepatitis C virus (HCV); hepatocellular carcinoma (HCC); C-X-C motif ligand 8 (CXCL8); proto-oncogene tyrosine-protein kinase Src (SRC)
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MDPI and ACS Style

Shabangu, C.S.; Siphepho, P.Y.; Li, C.-Y.; Cheng, W.-C.; Lu, M.-Y.; Huang, C.-F.; Yeh, M.-L.; Dai, C.-Y.; Huang, J.-F.; Chuang, W.-L.; Lin, Z.-Y.; Yu, M.-L.; Wang, S.-C. The Persistence of Hepatitis C Virus Infection in Hepatocytes Promotes Hepatocellular Carcinoma Progression by Pro-Inflammatory Interluekin-8 Expression. Biomedicines 2021, 9, 1446. https://doi.org/10.3390/biomedicines9101446

AMA Style

Shabangu CS, Siphepho PY, Li C-Y, Cheng W-C, Lu M-Y, Huang C-F, Yeh M-L, Dai C-Y, Huang J-F, Chuang W-L, Lin Z-Y, Yu M-L, Wang S-C. The Persistence of Hepatitis C Virus Infection in Hepatocytes Promotes Hepatocellular Carcinoma Progression by Pro-Inflammatory Interluekin-8 Expression. Biomedicines. 2021; 9(10):1446. https://doi.org/10.3390/biomedicines9101446

Chicago/Turabian Style

Shabangu, Ciniso S., Phumelele Y. Siphepho, Chia-Yang Li, Wei-Chung Cheng, Ming-Ying Lu, Chung-Feng Huang, Ming-Lun Yeh, Chia-Yen Dai, Jee-Fu Huang, Wan-Long Chuang, Zu-Yau Lin, Ming-Lung Yu, and Shu-Chi Wang. 2021. "The Persistence of Hepatitis C Virus Infection in Hepatocytes Promotes Hepatocellular Carcinoma Progression by Pro-Inflammatory Interluekin-8 Expression" Biomedicines 9, no. 10: 1446. https://doi.org/10.3390/biomedicines9101446

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