miR-539 enhances chemosensitivity to cisplatin in non-small cell lung cancer by targeting DCLK1.

摘要: Abstract microRNAs (miRNAs) have been implicated to play critical roles in non-small celllung cancer (NSCLC) progression and participate the regulation of drug resistance during chemotherapy. However, underlying molecular mechanism how miR-539 modulates chemosensitivity cisplatin (DDP) NSCLC cells remains largely unknown. In this study, we found that was significantly downregulated DDP-resistant cell lines (A549/DDP H1299/DDP). Overexpression enhanced sensitivity DDP by suppressing proliferation, causing cycle arrest, inducing apoptosis, repressing invasion migration. Whereas, downregulation inhibited parental promoting proliferation decreasing DDP-induced apoptosis. Furthermore, luciferase report assay identified doublecortin-like kinase 1 (DCLK1) a direct target miR-539. Knockdown DCLK1 mimicked function miR-539-mediated cells, while restoration reversed effect overexpression. We also P13 K/AKT/mTOR signaling pathway involved miR-539/DCLK1 axis -mediated cells. Additionally, closely correlated with severe clinicopathological parameters including upregulation DCLK1, DDP, tumor aggressiveness patients. conclusion, increased directly targeting which might provide potential biomarkers for therapy.