Roles of miRNAs in regulating ovarian cancer stemness

Abstract

Ovarian cancer is one of the gynaecology malignancies with the highest mortality rate. Ovarian cancer stem cell (CSC) is a subpopulation of ovarian cancer cells with increased self-renewability, aggression, metastatic potentials, and resistance to conventional anti-cancer therapy. The emergence of ovarian CSC is a critical factor that promotes treatment resistance and frequent relapse among ovarian cancer patients, leading to poor clinical outcomes. MicroRNA (miRNA) is a short, non-protein-coding RNA that regulates ovarian CSC development. Although multiple original research articles have discussed the CSC-regulatory roles of different miRNAs in ovarian cancer, there is a deficiency of a review article that can summarize the findings from different research papers. To narrow the gap in the literature, this review aimed to provide an up-to-date summary of the CSC-regulatory roles of various miRNAs in modulating ovarian cancer cell stemness. This review will begin by giving an overview of ovarian CSC and the pathways responsible for driving its appearance. Next, the CSC-regulatory roles of miRNAs in controlling ovarian CSC development will be discussed. Overall, more than 60 miRNAs have been reported to play CSC-regulatory roles in the development and progression of ovarian cancer. By targeting various downstream targets, these miRNAs can control the signaling activities of PI3K/AKT, EGFR/ERK, WNT/ß-catenin, NF-kß, Notch, Hippo/YAP, EMT, and DNA repair pathways. Hence, these CSC-modulatory miRNAs have the potential to be used as prognostic biomarkers in predicting the clinical outcomes of ovarian cancer patients. Targeting CSC-promoting miRNAs or increasing the expressions of CSC-repressing miRNAs can help slow ovarian cancer progression. However, more in-depth functional and clinical trials must be carried out to evaluate the suitability, safety, sensitivity, and specificity of these CSC-regulating miRNAs as prognostic biomarkers or therapeutic targets.

Keywords: CSC; Ovarian cancer; Prognostic biomarkers; Therapeutic agents; miRNAs.