Epigenetic modifications in bladder cancer: crosstalk between DNA methylation and miRNAs

Bladder cancer (BC) is a malignant tumor characterized by a high incidence of urinary system diseases. The complex pathogenesis of BC has long been a focal point in medical research. With the robust development of epigenetics, the crucial role of epigenetic modifications in the occurrence and progression of BC has been elucidated. These modifications not only affect gene expression but also impact critical biological behaviors of tumor cells, including proliferation, differentiation, apoptosis, invasion, and metastasis. Notably, DNA methylation, an important epigenetic regulatory mechanism, often manifests as global hypomethylation or hypermethylation of specific gene promoter regions in BC. Alterations in this methylation pattern can lead to increased genomic instability, which profoundly influences the expression of proto-oncogenes and tumor suppressor genes. MiRNAs, as noncoding small RNAs, participate in various biological processes of BC by regulating target genes. Consequently, this work aims to explore the interaction mechanisms between DNA methylation and miRNAs in the occurrence and development of BC. Research has demonstrated that DNA methylation not only directly influences the expression of miRNA genes but also indirectly affects the maturation and functionality of miRNAs by modulating the methylation status of miRNA promoter regions. Simultaneously, miRNAs can regulate DNA methylation levels by targeting key enzymes such as DNA methyltransferases (DNMTs), thereby establishing a complex feedback regulatory network. A deeper understanding of the crosstalk mechanisms between DNA methylation and miRNAs in BC will contribute to elucidating the complexity and dynamics of epigenetic modifications in this disease, and may provide new molecular targets and strategies for the early diagnosis, treatment, and prognostic evaluation of BC.