miR-149-5p promotes chemotherapeutic resistance in ovarian cancer via the inactivation of the Hippo signaling pathway

Abstract

Chemotherapeutic resistance remains a critical clinical issue is responsible for treatment failure in patients with ovarian cancer. Evidence of the involvement of miRNAs in chemoresistance in ovarian cancer has been recently emerging. However, the underlying molecular links between chemoresistance and miRNAs remain largely unknown. In this study, we report that miR-149-5p expression is markedly elevated in chemoresistant ovarian cancer tissues compared with the chemosensitive ovarian cancer tissues. Furthermore, the silencing of miR-149-5p enhanced the chemosensitivity of ovarian cancer cells to cisplatin in vitro and in vivo. Conversely, the upregulation of miR-149-5p aggravated chemoresistance in ovarian cancer cells. Our results further revealed that miR-149-5p directly targeted the core kinase components of the Hippo signaling pathway, STE20-like kinase (MST)1 and protein salvador homolog 1 (SAV1), resulting in the inactivation of TEA domain (TEAD) transcription. On the whole, our findings reveal a novel mechanism of of action miR-149-5p in inducing chemotherapeutic resistance in ovarian cancer, indicating that miR-149-5p may serve as a chemotherapeutic response indicator and a potential therapeutic target in ovarian cancer.