Abstract
BACKGROUND: Colon cancer-associated transcript-1 (CCAT1) has been demonstrated to act as an oncogene and promote chemoresistance in several cancers. However, little is known about the underlying mechanism of CCAT1 in cisplatin (DDP) resistance of non-small-cell lung cancer (NSCLC) cells. METHODS: qRT-PCR was performed to detect the expression levels of CCAT, miR-130a-3p, or sex-determining region Y-box 4 (SOX4) mRNA. Luciferase reporter assay, RNA immunoprecipitation (RIP), and qRT-PCR analysis were carried out to explore the potential targets of CCAT1 or miR-130a-3p. Effect of CCAT1, miR-130a-3p, or SOX4 on IC(50) value of DDP and ATP binding cassette subfamily G member 2 (ABCG2) level in NSCLC cells were determined by cell counting kits-8 (CCK-8) assay and western blot, respectively. RESULTS: CCAT1 and SOX4 were up-regulated, and miR-130a-3p was down-regulated in DDP-resistant NSCLC cells compared with their parental NSCLC cells. CCAT1 directly interacted with miR-130a-3p and negatively regulated miR-130a-3p expression. CCAT1 contributed to DDP resistance of A549/DDP cells by down-regulating miR-130a-3p. miR-130a-3p was found to directly target SOX4 to suppress its expression. SOX4 knockdown reversed miR-130a-3p-inhibition-induced increase of DDP resistance and ABCG2 expression in NSCLC cells. Exogenous expression of SOX4 abrogated CCAT1-knockdown-mediated decrease of DDP resistance and ABCG2 expression in DDP-resistant NSCLC cells. CONCLUSION: CCAT1/miR-130a-3p axis enhanced DDP resistance of NSCLC cells by targeting SOX4, providing potential targets to overcome DDP resistance and improve efficacy of chemotherapy for patients with NSCLC.