Rahimi-Farsi Nasim, Ghorbani Abozar, Mottaghi-Dastjerdi Negar, Shahbazi Taha, Bostanian Fatemeh, Mohseni Parvin, Yazdani Fateme
Department of Biology, University College of Nabi Akram, Tabriz, Iran.
Nuclear Agriculture Research School, Nuclear Science and Technology Research Institute (NSTRI), Karaj, Iran.
J Genet Eng Biotechnol. 2025 Mar;23(1):100471. doi: 10.1016/j.jgeb.2025.100471. Epub 2025 Feb 18.
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide. This study aimed to explore the role of hsa-miR-101-3p in HCC pathogenesis by identifying key genes and pathways. A comprehensive bioinformatics analysis revealed twelve hub genes (ETNK1, BICRA, IL1R1, KDM3A, ARID2, GSK3β, EZH2, NOTCH1, SMARCA4, FOS, CREB1, and CASP3) and highlighted their involvement in crucial oncogenic pathways, including PI3K/Akt, mTOR, MAPK, and TGF-β. Gene expression analysis showed significant overexpression of ETNK1, KDM3A, EZH2, SMARCA4, and CASP3 in HCC tissues, correlating with poorer survival outcomes. Drug screening identified therapeutic candidates, including Tazemetostat for EZH2 and lithium compounds for GSK3β, underscoring their potential for targeted treatment. These findings provide novel insights into the complexity of HCC pathogenesis, suggesting that the identified hub genes could serve as diagnostic or prognostic biomarkers and therapeutic targets. While bioinformatics-driven, this study offers a strong basis for future clinical validation to advance precision medicine in HCC.
肝细胞癌（HCC）是全球癌症相关死亡的主要原因。本研究旨在通过鉴定关键基因和通路来探索hsa-miR-101-3p在HCC发病机制中的作用。一项全面的生物信息学分析揭示了12个枢纽基因（ETNK1、BICRA、IL1R1、KDM3A、ARID2、GSK3β、EZH2、NOTCH1、SMARCA4、FOS、CREB1和CASP3），并强调了它们参与关键致癌通路，包括PI3K/Akt、mTOR、MAPK和TGF-β。基因表达分析显示，ETNK1、KDM3A、EZH2、SMARCA4和CASP3在HCC组织中显著过表达，与较差的生存结果相关。药物筛选确定了治疗候选药物，包括针对EZH2的他泽司他和针对GSK3β的锂化合物，强调了它们在靶向治疗方面的潜力。这些发现为HCC发病机制的复杂性提供了新的见解，表明所鉴定的枢纽基因可作为诊断或预后生物标志物及治疗靶点。虽然本研究是由生物信息学驱动的，但它为未来的临床验证提供了坚实基础，以推动HCC的精准医学发展。
