DNMT Enzymes and Their Impact on Cervical Cancer: A State-of-the-Art Review.

Genomic DNA methylation is an epigenetic modification that primarily occurs at CpG sites and is associated with the transcriptional repression of genes. This process plays a crucial role in maintaining cellular homeostasis and is catalyzed by a family of enzymes known as DNA methyltransferases (DNMTs), which includes DNMT1, DNMT2, DNMT3A, DNMT3B, and DNMT3L. DNMT1 is classified as a maintenance methyltransferase, whereas DNMT3A and DNMT3B are responsible for de novo methylation. Altered expression of DNMTs has been reported in various human diseases, including cancer. Cancer remains a major global health issue, with an estimated 20 million new cases and 9.7 million deaths reported in 2022. Among women, cervical cancer (CC) ranks fourth in both incidence and mortality worldwide, with persistent infection by high-risk human papillomavirus (HR-HPV) being the primary risk factor. Several studies have demonstrated that DNMT expression and activity are upregulated in CC, suggesting their potential as diagnostic and prognostic biomarkers. HR-HPV infection appears to increase DNMT expression, thereby promoting cervical carcinogenesis through aberrant methylation and subsequent silencing of tumor-suppressor genes such as PTEN, PAX1, and TSLC1. Furthermore, DNMTs are being explored as therapeutic targets in CC. In this review, we summarize the current state of the art regarding DNMTs in cervical cancer and discuss their functional roles and potential utility as diagnostic, prognostic, and therapeutic biomarkers.