RNA-binding proteins and exoribonucleases modulating miRNA in cancer: the enemy within

Recent progress in the investigation of microRNA (miRNA) biogenesis and the miRNA processing machinery has revealed previously unknown roles of posttranscriptional regulation in gene expression. The molecular mechanistic interplay between miRNAs and their regulatory factors, RNA-binding proteins (RBPs) and exoribonucleases, has been revealed to play a critical role in tumorigenesis. Moreover, recent studies have shown that the proliferation of hepatocellular carcinoma (HCC)-causing hepatitis C virus (HCV) is also characterized by close crosstalk of a multitude of host RBPs and exoribonucleases with miR-122 and its RNA genome, suggesting the importance of the mechanistic interplay among these factors during the proliferation of HCV. This review primarily aims to comprehensively describe the well-established roles and discuss the recently discovered understanding of miRNA regulators, RBPs and exoribonucleases, in relation to various cancers and the proliferation of a representative cancer-causing RNA virus, HCV. These have also opened the door to the emerging potential for treating cancers as well as HCV infection by targeting miRNAs or their respective cellular modulators. For many years, scientists have been investigating the complex world of miRNAs. These tiny molecules can bind to target mRNAs, influencing translation and broadly affecting gene expression. This review delves into the intricate processes that modulate the biogenesis and degradation/trimming of miRNAs, with a focus on RNA-binding proteins (RBPs) and exoribonucleases. The review also underscores the importance of these miRNA modulators in the proliferation of the hepatitis C virus (HCV), which can chronically lead to liver cancer. It discusses how certain RBPs and exoribonucleases interplay with liver-specific miR-122 and HCV RNA, offering new paths for therapeutic strategies against HCV. In summary, this review illuminates key evidence that RBPs and exoribonucleases affect miRNAs in various cancers. This comprehensive understanding could lead to advancements in how RBPs and exoribonucleases can be targeted in the therapeutic strategies of cancers.