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

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.

GPRC5A promotes paclitaxel resistance and glucose content in NSCLC

“…Cui et al . proved that circ_0002360 can regulate paclitaxel resistance in NSCLC through G protein-regulated inducer of neurite outgrowth 1 (GPRIN1) and GPRIN1 was overexpressed in paclitaxel-\resistant H1299 cell lines compared to the sensitive cells [37]. GNB2 was a guanine nucleotide-binding protein (G proteins), encoding for beta subunit.…”

CircTPST2 inhibits cisplatin sensitivity in head and neck squamous cell carcinoma by sponging miR-770-5p and interacting with Nucleolin

“…It was found that circRNAs play important roles in tumor malignancy, including tumor proliferation, metastasis, chemosensitivity, and radiosensitivity [22]. The mechanism of circRNA involvement in tumor chemotherapy sensitivity has been a hot topic in recent years, suggesting the potential of circRNAs as new tools to improve tumor chemosensitivity [23][24][25]. However, the role and mechanisms of circRNAs in HNSCC chemosensitivity remain elusive.…”

Progress in the studies on the molecular mechanisms associated with multidrug resistance in cancers

“…Many of them function as sponges and stabilizers of specific miRNAs because they have more than one site to recognize and bind specific miRNA; this function can reduce the number of functional miRNA and regulate the potential MDR-associated factors under regulation of this miRNA 103 , 104 , 105 , 106 , 107 , 108 . For example, circ_0002360 are found intimately linked to the development of drug resistance of NSCLC, through the potential mechanisms to modulate miR-585-3p/G protein regulated inducer of neurite outgrowth 1 (GPRIN1) axis 121 . Hsa_circ_0000277 promoted esophageal squamous cell carcinoma (ESCC) progression and cisplatin (DDP) resistance via modulating miR-873-5p/SOX4/Wnt/ β -catenin axis 122 .…”