Circular RNAcirc_0076305 Promotes Cisplatin (DDP) Resistance of Non-Small Cell Lung Cancer Cells by Regulating ABCC1 Through miR-186-5p.

Abstract

Background: Lung cancer is a social problem of increasing concern, and non-small cell lung cancer (NSCLC) accounts for 80%-85% incidence of lung cancer. Cisplatin (DDP) is reported as a first-line chemotherapy drug for NSCLC, but the resistance has became a main obstacle for NSCLC treatment. The high level of circular RNA circ_0076305 was related to the DDP resistance in NSCLC. However, the mechanism of circ_0076305 remains unclear in DDP resistance of NSCLC. Materials and Methods: Exosomes were detected by a transmission electron microscope and nanoparticle tracking analysis. The protein levels of CD63, CD81, P-glycoprotein (P-gp), Lung resistance-related protein, and ATP-binding cassette subfamily C member 1 (ABCC1) were examined by Western blot assay. Circ_0076305, microRNA-186-5p (miR-186-5p), and ABCC1 levels were tested by real-time quantitative polymerase chain reaction. DDP resistance was examined by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide assay. The binding relationship between miR-186-5p and circ_0076305 or ABCC1 was predicted by circRNA interactome or starBase, and then verified by dual-luciferase reporter and RNA immunoprecipitation assays. The effect of circ_0076305 on DDP resistance in NSCLC was examined by xenograft tumor model in vivo. Results: Circ_0076305 was increased in NSCLC cell-derived exosomes, DDP-resistant NSCLC tissues and cells. Circ_0076305 knockdown elevated DDP sensitivity in vitro. Mechanically, circ_0076305 enhanced ABCC1 expression through sponging miR-186-5p, thus regulating DDP resistance of NSCLC. Furthermore, circ_0076305 silencing improved DDP sensitivity of NSCLC in vivo. Conclusion: The results from this study disclosed that circ_0076305 knockdown improved DDP sensitivity by the miR-186-5p/ABCC1 axis in NSCLC, hinting a potential circRNA-targeted therapy for NSCLC.

• Authors: Xinli Wang, Hailiang Wang, Housen Jiang, Liang Qiao, Chunhong Guo
• Journal: Cancer biotherapy & radiopharmaceuticals (Cancer Biother Radiopharm) Vol. 38 Issue 5 Pg. 293-304 (Jun 2023) ISSN: 1557-8852 [Electronic] United States
• PMID: 34339285 (Publication Type: Journal Article)

Chemical References

• Cisplatin
• RNA, Circular
• MicroRNAs
• MIRN186 microRNA, human

Topics

• Humans
• Animals
• Carcinoma, Non-Small-Cell Lung (drug therapy, genetics)
• Cisplatin (pharmacology, therapeutic use)
• Lung Neoplasms (drug therapy, genetics)
• RNA, Circular (genetics)
• Disease Models, Animal
• MicroRNAs (genetics)
• Cell Proliferation
• Drug Resistance, Neoplasm (genetics)