MicroRNA Binding Site Polymorphisms in Hepatocellular Carcinoma: Implications for Pathogenesis, Prognosis, and Therapeutic Response.

Hepatocellular carcinoma (HCC) is a major global health challenge, characterized by complex molecular mechanisms. This review focuses on the crucial roles of microRNAs (miRNAs) in HCC development, progression, and therapeutic response. The regulation of gene expression and several critical cellular processes is carried out by miRNAs. These small, noncoding RNAs play a significant role in apoptosis, DNA repair, immune regulation, angiogenesis, cell migration, invasion, and tumor progression. MiRNAs have been identified as valuable noninvasive biomarkers, which suggests their potential use in early diagnosis, prognosis, and tracking the effectiveness of treatments. The relationship between single nucleotide polymorphisms (SNPs) in miRNA binding sites and their impact on both the vulnerability to and the development of HCC is also a topic of this discussion. These genetic variations can alter miRNA-mRNA interactions, affecting the expression of critical genes involved in HCC, which modulates key cellular processes such as apoptosis, DNA repair, and immune regulation. Emerging technologies like liquid biopsies and exosomal miRNA analysis are explored for their potential to revolutionize HCC diagnosis and treatment. This first-of-its-kind comprehensive review consolidates current findings on miRNA-SNP interactions across four major HCC pathogenic pillars (apoptosis, DNA repair, immune evasion, and metastasis), providing novel, noninvasive genetic biomarkers for HCC risk stratification, prognosis prediction, and tailoring individualized therapeutic regimens.