MiRNAs and their interplay with PI3K/AKT/mTOR pathway in ovarian cancer cells: a potential role in platinum resistance

Abstract

Ovarian cancer is a leading cause of death among gynecologic malignancies. This disappointing prognosis is closely related to intrinsic or acquired resistance to conventional platinum-based chemotherapy, which can affect a third of patients. As such, investigating relevant molecular targets is crucial in the fight against this disease. So far, many mutations involved in ovarian cancer pathogenesis have been identified. Among them, a few pathways were implicated. One such pathway is the P13K/AKT/mTOR with abnormalities found in many cases. This pathway is considered to have an instrumental role in proliferation, migration, invasion and, more recently, in chemotherapy resistance. Many miRNAs have been found to influence P13K/AKT/mTOR pathway with different potential role in tumor genesis and ovarian cancer behaviour. In particular, their biological function was recently investigated as regards chemoresistance, therefore, leading to the identification of potential specific indirect biomarker of platinum sensitivity in ovarian cancer.

Keywords: MicroRNA; Ovarian cancer; PI3K/AKT/mTOR pathway; Platinum resistance.

Fig. 1

Interplay between miRNAs and mTOR pathway. Figure schematically represents components of mTORC1 and mTORC2. a mTORC1 has mTOR, RAPTOR, DEPTOR, mLST8 and PRAS40. b mTORC2 contains mTOR, RICTOR, DEPTOR, mLST8 and SIN1. c TSC1 and TSC2 are involved in negative regulation of RHEB. miR-130a directly targeted TSC1 to promote ovarian cancer. d miR-497 and miR-199a quantitatively controlled mTOR to induce apoptosis in ovarian cancer cells