Long non coding RNA CCAT2 enhances proliferation, invasion and drug-resistances of non-small lung cancer via activating the miR-204-3p-suppresed IGFBP2/AKT/Bcl2 pathway

Abstract Background The treatment efficacy remains unsatisfactory due to the rapid progress, high rate of metastasis, and drug-resistance of NSCLS. It has been demonstrated that aberrant expression of long non coding RNA colon cancer-associated transcript 2 (CCAT2) in cells was closely related to tumorigenesis, tumor metastasis, and development of drug-resistance. The present study was aimed to thoroughly investigate the effect of CCAT2 in the growth of NSCLC and the underlying mechanisms, so that provide valuable theoretical basis for efficient treatment of NSCLC. Methods The expressions of CCAT2 and its target genes and downstream signals were respectively determined by Western-blot assay and RT-qPCR experiment. Cell growth of NSCLC cells was investigated using the CCK-8 kit while the proliferation assay was performed with the help of EDU staining. The NSCLC-bearing mice mode was established to evaluate the effect of PYCR1 on the progress of NSCLC and the underlying mechanisms in vivo. Results The CCAT2 was highly expressed in NSCLC tumor tissues and cells while not the corresponding normal ones. Further studies revealed that aberrant expression of CCAT2 in lung cancer signally contributed to proliferation, invasion, and migration of cancer cells and the progress of tumor tissues. Moreover, high level of CCAT2 dramatically down-regulated the cytotoxicity of cisplatin (DDP) to NSCLC cells and tissues by upregulation of the drug-resistance related proteins. Mechanisms studies displayed that upregulation of CCAT2 markedly decreased the miR-204-3p while contrary result was obtained when down-regulated the CCAT2 level. We further demonstrated that down-regulation of miR-204-3p level signally enhanced the activity of the insulin-like growth factor (IGF) signaling pathway. Conclusions The CCAT2 promoted the progress and drug-resistance of NSCLC thorough activation of the miR-204-3p suppressed IGFBP2/AKT/Bcl2 pathway, and may provide theoretical basis for improvement of therapy of NSCLC.