Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan.
J Transl Med. 2024 Mar 12;22(1):268. 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.
微小 RNA（miRNA）在基因表达和调控中发挥着关键作用，miRNA 功能失调与包括丙型肝炎病毒（HCV）相关肝细胞癌（HCC）在内的各种疾病有关。miRNA 和 mRNAs 之间在 HCV-HCC 中的调控关系仍存在认识上的差距。本研究旨在探讨持续性 HCV 诱导的 miRNA 表达对 HCC 基因调控的功能和影响。
使用 miRNA 芯片数据来鉴定差异表达的 miRNA 及其靶标，并通过 DIANA 分析 miRNA 参与的 KEGG 通路、基因本体论（GO）功能富集以及 IPA 分析的肝毒性、经典途径、相关网络功能和交互网络。
L-HCV 中有 17 个 miRNA 和 S-HCV 中有 9 个 miRNA 差异表达，L-HCV 中有 5 个 miRNA 和 S-HCV 中有 5 个 miRNA 在肝肝细胞癌（LIHC）肿瘤中显著表达。分组 miRNA 生存分析表明，L-HCV miRNAs 与 LIHC 的生存相关，miRNA-mRNA 靶标通过 LIHC 中的癌症途径调节病毒致癌和细胞周期改变。通过 miRNA-癌基因相互作用抑制 RCN1，抑制 RCN1 可抑制 HCC 侵袭和迁移。
持续性 HCV 感染诱导 miRNA 的表达，这些 miRNA 通过抑制 HCC 中的癌基因发挥肿瘤抑制作用。miRNA 上调的同时 RCN1 受到抑制，表明存在负相关关系。因此，hsa-miR-215-5p、hsa-miR-10b-5p、hsa-let-7a-5p 及其靶标 RCN1 可能是监测 HCV-HCC 进展的理想生物标志物。
