Zarlashat Yusra, Halász Judit, Dósa Edit
Department of Biochemistry, Government College University Faisalabad, Faisalabad 38000, Pakistan.
Department of Pathology, Forensic and Insurance Medicine, Semmelweis University, 1091 Budapest, Hungary.
Int J Mol Sci. 2025 Aug 28;26(17):8365. doi: 10.3390/ijms26178365.
Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide and the third leading cause of cancer-related death. Hyperactivation of oncogenes and suppression of tumor suppressor genes/proteins drive HCC initiation and progression. MicroRNAs (miRNAs) critically modulate HCC biology by regulating proliferation, apoptosis, and metastasis. Acting either as tumor suppressors or oncomiRs, they shape core signaling pathways, including PI3K/Akt/mTOR, Hippo-YAP/TAZ, Wnt/β-catenin, RAS/MAPK, and p53. Their dysregulation in tissues and body fluids renders them promising diagnostic biomarkers and therapeutic targets. Preclinical studies demonstrate that miRNA-based strategies-either restoring tumor-suppressive miRNAs (e.g., miR-34a, miR-125a-5p) or inhibiting oncogenic miRNAs (e.g., miR-660-5p)-can suppress HCC progression and reduce treatment resistance. Combination approaches, such as pairing miR-122 mimics with miR-221 inhibitors or delivering miR-326 via nanoparticles, further enhance efficacy by simultaneously targeting multiple oncogenic pathways. This review summarizes recent advances in miRNA-mediated regulation of HCC signaling and highlights their clinical potential, including ongoing trials of miRNA-based diagnostics and therapeutics for early detection, prognostication, and personalized treatment.
肝细胞癌（HCC）是全球最常见的恶性肿瘤之一，也是癌症相关死亡的第三大主要原因。癌基因的过度激活和肿瘤抑制基因/蛋白的抑制驱动了HCC的发生和发展。微小RNA（miRNA）通过调节细胞增殖、凋亡和转移，对HCC生物学特性起着关键的调节作用。它们作为肿瘤抑制因子或致癌miRNA，塑造了包括PI3K/Akt/mTOR、Hippo-YAP/TAZ、Wnt/β-连环蛋白、RAS/MAPK和p53在内的核心信号通路。它们在组织和体液中的失调使其成为有前景的诊断生物标志物和治疗靶点。临床前研究表明，基于miRNA的策略——恢复肿瘤抑制性miRNA（如miR-34a、miR-125a-5p）或抑制致癌性miRNA（如miR-660-5p）——可以抑制HCC进展并降低治疗耐药性。联合方法，如将miR-122模拟物与miR-221抑制剂配对或通过纳米颗粒递送miR-326，通过同时靶向多个致癌途径进一步提高疗效。本综述总结了miRNA介导的HCC信号调节的最新进展，并强调了它们的临床潜力，包括正在进行的基于miRNA的诊断和治疗用于早期检测、预后评估和个性化治疗的试验。
