MALAT1 promotes cisplatin resistance in cervical cancer by activating the PI3K/AKT pathway.

Abstract

To investigate the role of MALAT1 in the cisplatin treatment of cervical cancer and its underlying mechanism. The effects of different doses of cisplatin on the proliferation and apoptosis of cervical cancer cells were detected by cell counting kit-8 (CCK-8) assay and apoptosis assay, respectively. We used bioinformatics methods to predict the downstream genes of MALAT1 and examined the expression relationship between the target gene BRWD1 and MALAT1 by quantitative Real-time polymerase chain reaction (qRT-PCR). Western blot was performed to detect the expression levels of apoptosis-related proteins and key genes in PI3K/AKT signaling pathway. After MALAT1 was knocked down, cisplatin showed an inhibited effect on the proliferation of HeLa and C-33A cells in a concentration-dependent manner. After treatment of cervical cancer cells with 5 μM cisplatin, MALAT1 knockdown enhanced the apoptosis of HeLa and C-33A cells, and up-regulated expression of cleaved caspase-3. Over-expression of MALAT1 in cells showed the opposite results. Starbase website was used to predict that MALAT1 might regulate BRWD1 expression. Over-expression of MALAT1 significantly up-regulated the mRNA expression of BRWD1 in HeLa and C-33A cells. After knockdown of BRWD1, cisplatin markedly decreased the proliferation of HeLa and C-33A cells, and promoted cell apoptosis and cleaved caspase-3 expression. Besides, HeLa and C-33A cells showed increased expressions of p-PI3K and p-AKT after MALAT1 was up-regulated. MALAT1 promoted the cisplatin resistance of cervical cancer, which might be related to regulation of cell apoptosis via BRWD1 and PI3K/AKT pathway.