MALAT1-miR-101-SOX9 feedback loop modulates the chemo-resistance of lung cancer cell to DDP via Wnt signaling pathway

Abstract

Cisplatin (DDP)-based chemotherapy is a standard strategy for lung cancer, while chemoresistance remains a major therapeutic challenge. Recent evidence highlights the crucial regulatory roles of long non-coding RNAs (lncRNA) in tumor biology. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has important roles in regulating the proliferation, invasion and migration of lung cancer cell. High MALAT1 expression in lung cancer was related to poorer clinicopathologic features in this study. MALAT1 knockdown alone was sufficient to amplify DDP-induced repression of cell viability. MALAT1 knockdown could also sensitized DDP-resistant lung cancer cells (A549/DDP and H1299/DDP) to DDP. Further assays indicated that MALAT1 acted as a competing endogenous RNA to upregulate SOX9 expression by sponging miR-101 in DDP-resistant cancer cells, through Wnt signaling pathway. Moreover, SOX9 could bind to the promoter of MALAT1 to activate its transcription. Taken together, MALAT1, miR-101 and SOX9 form a feedback loop to enhance the chemo-resistance of lung cancer cell to DDP; this MALAT1-miR-101-SOX9 feedback loop plays an important role in the chemo-resistance of lung cancer cell to DDP and may serve as a potential target for cancer treatment.