P1.03-34 The lncRNA NEAT1 Promotes Radioresistance via the MiR-491-5p/CAPG Axis in NSCLC

Abstract

Long noncoding RNAs (lncRNAs) have been implicated in various biological processes and pathological conditions in cancer. However, the exact roles of LncRNA NEAT1 and its underlying mechanisms in radio resistance of non-small cell lung cancer (NSCLC) remain largely unclear. The expression of LncRNA NEAT1 was measured in NSCLC tissues and cell lines by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The radio sensitivity of NSCLC cells including H358, H226, HCC827, H1975, H1395 and H23 were detected by colony formation. Lentivirus-mediated short hairpin RNAs were used to knock down NEAT1 expression in H358 cells. Furthermore, the role of NEAT1 on tumor cell biological behavior and radio resistance were explored through MTT, colony formation, transwell migration, and invasion assays in vitro. Luciferase reporter assay was used to verify interaction between miR-491-5p and NEAT1, CAPG. The potential mechanism of LncRNA NEAT1 was identified by Western blot. Additionally, the association between the survival time and miR-491-5p expression in lung adenocarcinoma patients were evaluated based on the TCGA data. NEAT1 was highly expressed in NSCLC tissues and cell lines. NEAT1 was up-expressed in radiosensitive NSCLC cells and low-expressed in radioresistant NSCLC cells. Conversely, miR-491-5P was low-expressed in radiosensitive NSCLC cells and up-expressed in radioresistant NSCLC cells. In addition, we revealed a reciprocal repression between NEAT1 and miR-491-5P. CAPG was identified as a down-stream target of miR-491-5P. Further experiments revealed that lncRNA NEAT1 silencing inhibited cell proliferation, invasion and radio resistance in vitro. Overexpression of CAPG rescued the effects of NEAT1 downregulation on proliferation, invasion and radio resistance. In addition, mechanistic analysis showed that lncRNA NEAT1 upregulated the miR-491-5p-targeted gene CAPG through acting as a competitive “sponge” of miR-491-5p. By cox regression analysis, a tendency towards a survival benefit in patients with high miR-491 expression was observed in 430 lung adenocarcinoma patients of the TCGA database. Our findings suggest that NEAT1 regulated proliferation, invasion and radio resistance by modulating the miR-491-5p/CAPG axis in NSCLC.