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… Click to show full 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.
               
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