Noncoding RNAs and DNA methylation as epigenetic modulators of breast cancer: mechanisms and clinical perspectives in the Iranian population, a systematic review

Noncoding RNAs (ncRNAs), including microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs), play critical epigenetic roles in regulating gene expression and cancer development. Dysregulation of these molecules is closely associated with breast cancer initiation, progression, metastasis, and therapeutic resistance. Another major epigenetic mechanism, DNA methylation, also contributes to cancer susceptibility. Following PRISMA guidelines, a systematic search was conducted in PubMed, Scopus, IranMedex, and Magiran for studies published between 2019 and 2024. Eligible studies investigated the roles of ncRNAs and/or DNA methylation in breast cancer. Data extraction and study selection were performed according to predefined inclusion criteria. The study identified several dysregulated ncRNAs, including miR-155, miR-605, ZEB2-AS1, MALAT1, AK058003, SGO-AS1, and circ_0005046, that regulate key cellular processes including apoptosis, proliferation, invasion, and therapy resistance. Additionally, aberrant DNA methylation of genes such as PGR, ISL1, and MGMT was associated with altered gene expression and an increased risk of breast cancer. Both ncRNAs and DNA methylation demonstrate strong potential as diagnostic and prognostic biomarkers with clinical relevance in breast cancer. To our knowledge, this is the first systematic review to integrate findings from both international and Iranian studies, providing a comprehensive overview of epigenetic regulation in breast cancer.