Knockdown of MALAT1 enhances chemosensitivity of ovarian cancer cells to cisplatin through inhibiting the Notch1 signaling pathway

Abstract

Long non-coding RNAs (lncRNAs) are critical regulators in chemoresistance of various tumors including ovarian cancer. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been reported to be upregulated and contributed to ovarian cancer tumorigenesis. The aim of this study was to explore the roles of MALAT1 and the underlying molecular regulatory mechanism in the chemoresistance of ovarian cancer cells. Our data demonstrated that MALAT1 and Notch1 mRNA were upregulated in ovarian cancer tissues, as well as cisplatin (CDDP)-resistant ovarian cancer cells. A positive correlation between MALAT1 and Notch1 mRNA expression was observed. MALAT1 knockdown significantly attenuated CDDP resistance, and enhanced CDDP-induced apoptosis in CDDP-resistant ovarian cancer cells. MALAT1 knockdown enhanced CDDP-induced apoptosis in vivo, as indicated by upregulation of Bax protein expression and downregulation of Bcl-2 protein expression. Additionally, MALAT1 knockdown inhibited the Notch1 pathway and ABCC1 expression in CDDP-resistant ovarian cancer cells. MALAT1 was demonstrated to interact with Notch1. Notch1 knockdown attenuated CDDP resistance, and downregulated the protein expression of ABCC1 in ovarian cancer cells. Taken together, our findings suggested that knockdown of MALAT-1 enhanced chemosensitivity of ovarian cancer cells to CDDP through inhibiting Notch1 signaling pathway.

Keywords: ABCC1; Chemosensitivity; Cisplatin; MALAT1; Notch1; Ovarian cancer.