LncRNA CASC2 inhibits autophagy and promotes apoptosis in non-small cell lung cancer cells via regulating the miR-214/TRIM16 axis

Background: Dysregulated long noncoding RNAs (lncRNAs) have been frequently observed in various cancers including non-small cell lung cancer (NSCLC) and are closely associated with cancer progression. Previous studies also found that low expression of lncRNA cancer susceptibility candidate 2 (CASC2) functioned as a tumor suppressor in NSCLC. Our study aimed to explore the detailed molecular mechanism of CASC2 involved in NSCLC progression. Methods: The expressions of CASC2, tripartite motif-containing protein 16 (TRIM16) and miR-214 in NSCLC tissues and cells were detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) or western blot. Flow cytometry analysis was performed to evaluate apoptosis. Autophagy was assessed using green fluorescent protein microtubule-associated protein 1 light chain 3α (GFP-LC3) puncta analysis, acridine orange (AO) staining and western blot. Luciferase reporter assay, RNA immunoprecipitation (RIP), RNA pull-down and immunofluorescence staining were employed to explore the association between CASC2, TRIM16 and miR-214. Results: CASC2 and TRIM16 expressions were significantly downregulated and miR-214 expression was dramatically upregulated in NSCLC tissues and cells. Overexpression of CASC2 induced apoptosis and inhibited autophagy in NSCLC cells. miR-214 was bound to CASC2 and its knockdown reversed the regulatory effect of CASC2 inhibition on apoptosis and autophagy in NSCLC cells. Moreover, TRIM16 was validated as a target of miR-214 and its interference attenuated miR-214 knockdown-mediated promotion of apoptosis and inhibition of autophagy. Besides, CASC2 enhanced TRIM16 expression through functioning as a competing endogenous RNA (ceRNA) for miR-214 in NSCLC cells. Conclusion: lncRNA CASC2 inhibited autophagy and promoted apoptosis in NSCLC cells via regulating the miR-214/TRIM16 axis, shedding light on the mechanism underlying NSCLC carcinogenesis.