Circular RNA circ_0002360 regulates the Taxol resistance and malignant behaviors of Taxol-resistant non-small cell lung cancer cells by microRNA-585-3p-dependent modulation of G protein regulated inducer of neurite outgrowth 1

Abstract

ABSTRACT Drug resistance has become the major obstacle for the treatment of non-small cell lung cancer (NSCLC). Circular RNAs (circRNAs) are tightly linked to the development of drug resistance of NSCLC. Herein, we tested the function of circ_0002360 in the Taxol resistance of NSCLC. Circ_0002360, microRNA (miR)-585-3p and G protein regulated inducer of neurite outgrowth 1 (GPRIN1) were quantified by quantitative real-time PCR (qRT-PCR). To identify the circular structure of circ_0002360, RNase R digestion was applied. To detect cell proliferation, colony formation and 5-ethynyl-2’-deoxyuridine (EdU) assays were used. For assessment of cell apoptosis, flow cytometry was adopted. For motility and invasion analyses, transwell assay was employed. Our data showed that circ_0002360 was mainly located in the cytoplasm and was highly expressed in the Taxol-resistant NSCLC. Silencing of circ_0002360 inhibited cell Taxol resistance, proliferation, motility, and invasiveness and induced apoptosis in vitro. MiR-585-3p was underexpressed in Taxol-resistant NSCLC and was targeted by circ_0002360. MiR-585-3p knockdown alleviated the influence of circ_0002360 silence on Taxol-resistant cells. GPRIN1 was directly targeted by miR-585-3p. The influence of miR-585-3p on cell Taxol resistance and functional behaviors was reversed by GPRIN1 overexpression. Moreover, circ_0002360 modulated GPRIN1 through miR-585-3p. Additionally, silencing of circ_0002360 weakened the growth of xenografts in vivo. Our study demonstrated that silencing of circ_0002360 enhanced the Taxol sensitivity and suppressed the malignant behaviors of Taxol-resistant NSCLC cells by miR-585-3p/GPRIN1 axis, providing novel targets for improving the anti-tumor efficacy of Taxol in NSCLC.