Role of microRNAs in cisplatin response of cancer stem cells

Cisplatin (CDDP)-based chemotherapy remains a cornerstone of cancer treatment, but its efficacy is often limited by the development of chemo resistance that is mainly associated with cancer stem cells (CSCs). MicroRNAs (miRNAs) have emerged as pivotal post-transcriptional regulators of gene expression, critically influencing key cellular processes, including drug response. This review aims to provide a comprehensive analysis of the current evidence elucidating the role of specific miRNAs in governing the CDDP response of CSCs. We conducted a systematic assessment of all available scientific literature databases up to (Nov 2025) to identify relevant studies. Our analysis reveals that miRNAs function as a dynamic network, either promoting or reducing CDDP resistance in CSCs through regulation of signaling pathways, apoptosis, DNA repair pathways, and ABC drug transporters. We identified several consistently reported oncomiRs (e.g., miR-21, miR-765, and miR-132) that were up regulated in CSCs and confer CDDP resistance. Conversely, tumor-suppressor miRNAs were frequently down regulated and their re-expression re-sensitized CSCs to CDDP. This comprehensive review consolidates the compelling evidence that miRNAs are central regulators of CDDP response in CSCs. Understanding this intricate regulatory network provides a robust foundation for developing novel therapeutic strategies, such as miRNA-based mimics or inhibitors (anti-miRs) to overcome CDDP resistance in CSCs improve patient outcomes.