ABSTRACT
BACKGROUND: Breast cancer, the deadliest disease affecting women globally, exhibits heterogeneity with distinct molecular subtypes. Despite advances in cancer therapy, the persistence of high mortality rates due to chemotherapy resistance remains a major challenge. Lipoic acid (LA), a natural antioxidant, has proven potent anticancer properties. Yet, the impact of LA on microRNA (miRNA) expression profile in breast cancer remains unexplored. AIM: The aim of this study was to unravel the effect of LA on miRNA expression profiles in different breast cancer cell lines. METHODS: The MiRCURY LNA miRNA miRNome qPCR Panel was used to compare the miRNA signature in MDA-MB-231 and MCF-7 cells treated or not with LA. RESULTS: We identified six upregulated and six downregulated miRNAs in LA-treated MDA-MB-231 cells and 14 upregulated and four downregulated miRNAs in LA-treated MCF-7 cells compared to control cells. KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis revealed that the deregulated miRNAs could alter different signaling cascades including FoxO, P53 and Hippo pathways. CONCLUSION: The outcome of this study provides further insights into the molecular mechanisms underlying the therapeutic benefit of LA. This in turn could assist the amelioration of LA-based anticancer therapies.
Subject(s)
Breast Neoplasms , Gene Expression Regulation, Neoplastic , MicroRNAs , Thioctic Acid , Humans , Thioctic Acid/pharmacology , MicroRNAs/genetics , MicroRNAs/metabolism , Breast Neoplasms/genetics , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Breast Neoplasms/metabolism , Female , Gene Expression Regulation, Neoplastic/drug effects , MCF-7 Cells , Cell Line, Tumor , Antioxidants/pharmacology , Gene Expression Profiling/methods , Signal Transduction/drug effects , Transcriptome/drug effectsABSTRACT
MicroRNAs, short non-coding single-stranded RNAs, are important regulators and gatekeepers of the coding genes in the human genome. MicroRNAs are highly conserved among species and expressed in different tissues and cell types. They are involved in almost all the biological processes as apoptosis, proliferation, cell cycle arrest and differentiation. Playing all these roles, it is not surprising that the deregulation of the microRNA profile causes a number of diseases including cancer. Breast cancer, the most commonly diagnosed malignancy in women, accounts for the highest cancer-related deaths worldwide. Different microRNAs were shown to be up or down regulated in breast cancer. MicroRNAs can function as oncogenes or tumor suppressors according to their targets. In this review, the most common microRNAs implicated in breast cancer are fully illustrated with their targets. Besides, the review highlights the effect of exosomal microRNA on breast cancer and the effect of microRNAs on drug and therapies resistance as well as the miRNA-based therapeutic strategies used until today.
