Systematic integration of molecular and clinical approaches in HCV-induced hepatocellular carcinoma

• Published in: Journal of translational medicine 2024-03, Vol.22 (1), p.268-14, Article 268
• Main Authors: Shabangu, Ciniso Sylvester, Su, Wen-Hsiu, Li, Chia-Yang, Yu, Ming-Lung, Dai, Chia-Yen, Huang, Jee-Fu, Chuang, Wan-Long, Wang, Shu-Chi
• Format: Article
• Language: English
• Subjects: Antibodies; Antigens; Biomarkers; Carcinogenesis; Carcinoma, Hepatocellular - genetics; Cell cycle; Development and progression; Gene expression; Gene Expression Profiling; Gene regulation; Genes; Genomes; HCC; HCV; Health aspects; Health maintenance organizations; Hepacivirus - genetics; Hepatitis C; Hepatitis C virus; Hepatocellular carcinoma; Hepatoma; Hepatotoxicity; Humans; Infections; International economic relations; Liver cancer; Liver cirrhosis; Liver Neoplasms - genetics; Messenger RNA; MicroRNA; MicroRNAs; MicroRNAs - genetics; miRNA; Oncogenes; Patients; RCN1; RNA, Messenger - genetics; Scientific equipment and supplies industry; Software; Viral infections
• ISSN: 1479-5876; 1479-5876
• DOI: 10.1186/s12967-024-04925-1

MicroRNAs (miRNAs) play a crucial role in gene expression and regulation, with dysregulation of miRNA function linked to various diseases, including hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC). There is still a gap in understanding the regulatory relationship between miRNAs and mRNAs in HCV-HCC. This study aimed to investigate the function and effects of persistent HCV-induced miRNA expression on gene regulation in HCC. MiRNA array data were used to identify differentially expressed miRNAs and their targets, and miRNAs were analyzed via DIANA for KEGG pathways, gene ontology (GO) functional enrichment, and Ingenuity Pathways Analysis (IPA) for hepatotoxicity, canonical pathways, associated network functions, and interactive networks. Seventeen miRNAs in L-HCV and 9 miRNAs in S-HCV were differentially expressed, and 5 miRNAs in L-HCV and 5 miRNAs in S-HCV were significantly expressed in liver hepatocellular carcinoma (LIHC) tumors. Grouped miRNA survival analysis showed that L-HCV miRNAs were associated with survival in LIHC, and miRNA‒mRNA targets regulated viral carcinogenesis and cell cycle alteration through cancer pathways in LIHC. MiRNA-regulated RCN1 was suppressed through miRNA-oncogene interactions, and suppression of RCN1 inhibited invasion and migration in HCC. Persistent HCV infection induced the expression of miRNAs that act as tumor suppressors by inhibiting oncogenes in HCC. RCN1 was suppressed while miRNAs were upregulated, demonstrating an inverse relationship. Therefore, hsa-miR-215-5p, hsa-miR-10b-5p, hsa-let-7a-5p and their target RCN1 may be ideal biomarkers for monitoring HCV-HCC progression.