CircRNA B cell linker regulates cisplatin sensitivity in nonsmall cell lung cancer via microRNA-25-3p/BarH‑like homeobox 2 axis.

Abstract

Cisplatin (DDP) was a commonly used drug in the treatment of nonsmall cell lung cancer (NSCLC). However, the current resistance of patients to DDP seriously affected its therapeutic effect. Circular RNAs (circRNAs) have been reported to regulate drug resistance in cells. The purpose of this paper is to study the effect of circRNA B cell linker (circ_BLNK) in DDP resistance of NSCLC. The abundances of circ_BLNK, microRNA-25-3p (miR-25-3p) and BarH‑like homeobox 2 (BARX2) were examined by quantitative real-time PCR and western blot analysis. Cell proliferation and apoptosis were detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay, EdU assay and flow cytometry. Transwell assay was applied to assess cell migration and invasion. Protein levels were quantified by western blot analysis. Dual-luciferase reporter assay was enforced to confirm the links among circ_BLNK, miR-25-3p and BARX2. The mice models were enforced to evaluate tumorigenicity. Herein, circ_BLNK and BARX2 were lower-expressed, whereas miR-25-3p was higher-expressed in A549/DDP and H1299/DDP cells than their homologous parental NSCLC cells. Circ_BLNK increases improved DDP sensitivity of NSCLC cells by promoting cell apoptosis and inhibiting proliferation, migration and invasion. Moreover, we confirmed that circ_BLNK regulated BARX2 by inhibiting miR-25-3p. Accordingly, overexpression of circ_BLNK improved DDP sensitivity of NSCLC cells via miR-25-3p/BARX2 axis. Besides, circ_BLNK reduced cell resistance to DDP, thereby inhibiting tumor development in mice. Circ_BLNK promoted the DDP sensitivity of NSCLC via regulating miR-25-3p/BARX2 axis.