ABSTRACT
Lung adenocarcinoma (LUAD) is the most common type of lung cancer. Currently, the survival rate of LUAD patients remains low due to heterogeneity and high invasiveness. The long non-coding RNA (lncRNA) cancer susceptibility candidate 2 (CASC2) is reported to be related to LUAD development. Hence, we investigate the roles and regulatory mechanism of CASC2 in LUAD. The expression levels of CASC2, microRNA (miR)-21, and p53 were quantified by quantitative real-time polymerase chain reaction, and the protein levels of Bax, Bcl-2, p53, and p21 were examined using western blotting. A dual-luciferase reporter experiment was conducted to prove the molecular interactions between CASC2 and miR-21 or p53. CCK-8 and flow cytometry assays were conducted to assess cell proliferation and apoptosis, respectively. CASC2 was expressed at a low level in LUAD patients and LUAD cell lines. CASC2 overexpression markedly suppressed cell proliferation and enhanced apoptosis. Mechanistically, CASC2 overexpression dramatically inhibited miR-21 expression and increased p53 expression by directly targeting miR-21. Moreover, rescue experiments suggested that either miR-21 overexpression or p53 silencing obviously weakened the biological effects of CASC2 overexpression. In addition, p53 was proven to be an upstream transcription factor of CASC2 and can activate CASC2 transcription. These results provide evidence that the lncRNA CASC2/miR-21/p53 form a positive feedback loop to mediate cell proliferation and apoptosis in LUAD, which may provide a new insight into the pathological mechanisms of LUAD.
