Epigenetic Regulation in Chemotherapy Resistance of Breast Cancer: Role of Chromatin Modifications and Non-Coding RNAs in Chemotherapeutic Resistance

Chemotherapy is the main systemic treatment approach to breast cancer. But chemotherapy resistance is one of the main drawbacks in breast cancer treatment nowadays. In this respect, the role of epigenetic control and non-coding RNAs leading to the development of chemoresistance will be presented here. The information about epigenetic changes in each cell, particularly concerning drug metabolism, DNA repair, apoptotic gene expression, and drug efflux, enhances the effectiveness of drugs by increasing chemosensitivity. This is achieved through mechanisms such as DNA methylation, histone modifications, and chromatin remodeling. At the same time, non-coding RNAs, particularly microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), also regulate these pathways by targeting key genes of the chemosensitivity network. In this review, epigenetic and non-coding RNA-based chemoresistance mechanisms are described with a specific focus on chromatin-based mechanisms and miRNAs, lncRNAs, and circular RNA. Like, overexpression of miR-34a and miR-125b shows reduced resistance in breast cancer cells, with the association of different drugs like docetaxel and paclitaxel. Additionally, upregulation of miR-125 targets the UTR (Untranslated region) of the p53 gene to inhibit translation. In the EMT pathway, overexpression of miR-21 and miR-155 resulted in suppression of different genes, promoting tumorigenesis, metastasis, etc. On the other hand, lncRNAs like H19 induce autophagy and inhibit breast cancer cells from undergoing the EMT (Epithelial-to-mesenchymal transition) pathway. Another lncRNA, HOTAIR expression helps to promote tumor growth, invasion, and other processes. It also suggests therapeutic methodologies directed at the epigenetic regulators and non-coding RNAs to overcome chemoresistance. Perseverant research on these regulatory mechanisms might help come out with personalized and streamlined treatment protocols in the management of breast cancer.