Hongyan ZHU, Wenshu YANG, Qingping CHENG, Shuai YANG

Circ_0010235 Regulates HOXA10 Expression to Promote Malignant Phenotypes and Radioresistance in Non-small Cell Lung Cancer Cells Via Decoying miR-588

Background: Circular RNAs (circRNAs) are key modulators in carcinogenesis and radioresistance in multiple kinds of human cancers. Aims: To explore the role of circ_0010235 in non-small cell lung cancer (NSCLC).Study Design: Cell culture study and animal study. Methods: The detection of circ_0010235, microRNA-588 (miR-588), and homeobox protein A10 (HOXA10) was implemented via reverse transcription-quantitative polymerase chain reaction (RT-qPCR). CCK-8, EdU, flow cytometry, transwell, and wound healing assays. These strategies were applied to evaluate cell functions. The western blot technique was employed for protein examination. The colony formation assay was used to determine cell survival after radiation treatment. In vivo research was performed by tumor xenograft assay. The binding analysis was also carried out through dual-luciferase reporter and RNA immunoprecipitation studies. Results: Circ_0010235 had an enhanced expression in NSCLC. Circ_0010235 deficiency inhibited cell proliferation, invasiveness, and migratory ability but promoted apoptosis and radiosensitivity. Downregulation of circ_0010235 decelerated tumor growth and promoted radiation sensitivity in vivo. Circ_0010235 was controlled biologically in NSCLC cells by combining with miR-588 and targeting miR-588. HOXA10 acted as a target of miR-588. MiR 588 upregulation inhibited NSCLC cell malignant phenotypes and elevated radiosensitivity via downregulating HOXA10. Circ_0010235 could regulate the level of HOXA10 by sponging miR-588. Conclusion: Circ_0010235 contributed to the malignant progression of NSCLC, but suppressed the radiation sensitivity via targeting miR 588 to induce HOXA10 upregulation.

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