Circ_0072088 knockdown contributes to cisplatin sensitivity and inhibits tumor progression by miR-944/LASP1 axis in non-small cell lung cancer.

Abstract

Non-small cell lung cancer (NSCLC) is an aggressive tumor that accounts for a large proportion of cancer-related deaths. Cisplatin (CDDP) has been utilized to treat NSCLC. However, the efficacy of CDDP is usually restrained owing to the development of drug resistance. This study aims to reveal the molecular mechanism of the resistance of NSCLC cells to CDDP. The expression levels of circRNA_0072088 (circ_0072088), microRNA-944 (miR-944), and LIM and SH3 protein 1 (LASP1) were measured by quantitative real-time PCR (qRT-PCR) in CDDP-resistant NSCLC tissues and cells. Protein expression was determined by Western blotting in CDDP-resistant NSCLC tissues and cells. The functional effects of circ_0072088, miR-944, and LASP1 on CDDP sensitivity and NSCLC progression were revealed by Cell Counting Kit-8 (CCK-8), flow cytometry, cell colony formation, wound healing, and transwell invasion assays. The binding relationship between miR-944 and circ_0072088 or LASP1 was identified by a dual-luciferase reporter and RNA immunoprecipitation assay. The effects of circ_0072088 knockdown on tumor growth in vivo were analyzed by an in vivo tumor formation assay. Circ_0072088 and LASP1 expression were significantly upregulated, while miR-944 expression was downregulated in CDDP-resistant NSCLC tissues and cells as compared with control groups. Circ_0072088 expression was significantly associated with tumor-node-metastasis stage and tumor size. Functionally, circ_0072088 knockdown improved CDDP sensitivity and repressed NSCLC cell malignancy, whereas miR-944 inhibitor hindered these effects. Mechanistically, circ_0072088 functioned as a sponge for miR-944 and miR-944 targeted LASP1. Circ_0072088 knockdown improved the sensitivity of tumor to CDDP in vivo. Circ_0072088 silencing improved CDDP sensitivity and inhibited NSCLC progression by downregulating LASP1 expression through sponging miR-944. These data provide novel insight into the resistance of NSCLC to CDDP.