NSUN2-mediated RNA methylation: Molecular mechanisms and clinical relevance in cancer

Cancer remains a leading cause of morbidity and mortality worldwide, necessitating the ongoing investigation of molecular targets for improved diagnosis, prognosis, and therapy. Among these targets, RNA modifications, particularly N5-methylcytosine (m5C) in RNA, have emerged as critical regulators of gene expression and cellular functions. NOP2/Sun RNA methyltransferase family member 2 (NSUN2) is a key enzyme in m5C modification, significantly influencing various biological processes and tumorigenesis. NSUN2 methylates multiple RNA species, including transfer RNAs (tRNAs), messenger RNAs (mRNAs), and non-coding RNAs, impacting RNA stability, translation efficiency, and cellular stress responses. These modifications, in turn, affect cell proliferation, differentiation, and survival. In cancer, NSUN2 is frequently upregulated, associated with aggressive tumor phenotypes, poor prognosis, and therapy resistance. Its role in oncogenic signaling pathways further underscores its importance in cancer biology. This review offers a comprehensive overview of NSUN2's role in cancer, focusing on its involvement in RNA methylation and its implications for tumor initiation and progression. Additionally, we explore the potential of NSUN2 as a biomarker for cancer diagnosis and prognosis, and its promise as a therapeutic target.