Circ_0018534 Promotes Non-Small Cell Lung Cancer Progression by Upregulating BTBD7 via Sponging miR-153-3p

Abstract

Background: Non-small cell lung cancer (NSCLC) is the most common malignant tumor in lung. In this study, we aimed to explore the role and underlying mechanism of circular RNA 0018534 (circ_0018534) in NSCLC progression.Methods: Real-time quantitative PCR (RT-qPCR) was used to detect the expression of circ_0018534, microRNA-153-3p (miR-153-3p) and BTB/POZ domain-containing protein 7 (BTBD7) in NSCLC tissues and cells. Protein expression was measured by western blot analysis. The morphological features of obtained NSCLC patient tissues were observed by haematoxylin and eosin staining assay. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT), 5-Ethynyl-29-deoxyuridine, flow cytometry analysis, and transwell migration and invasion assays were used to examine cell viability, proliferation, apoptosis, migration and invasion, respectively. Bioinformatics analysis and dual-luciferase reporter assay were carried out to determine the interaction among circ_0018534, miR-153-3p and BTBD7. Furthermore, lentivector for short hairpin RNA against circ_0018534 (sh-circ_0018534) was used to decrease circ_0018534 expression in an animal tumor model.Results: Circ_0018534 and BTBD7 expression were significantly increased, whereas miR-153-3p expression was decreased in NSCLC tissues and cells. Circ_0018534 downregulation markedly alleviated cell proliferation, migration, invasion, and elevated cell apoptosis in NSCLC cells in vitro. MiR-153-3p inhibitors partially reversed the effects of circ_0018534 knockdown on cell proliferation, migration, invasion and apoptosis in NSCLC. Moreover, miR-153-3p could directly target BTBD7, and circ_0018534 promoted BTBD7 expression by targeting miR-153-3p. Besides, BTBD7 overexpression attenuated miR-153-3p mimics-mediated effects on NSCLC cell progression. Furthermore, circ_0018534 deletion suppressed NSCLC tumor growth in vivo.Conclusion: Our results demonstrated that circ_0018534 might contribute to the progression of NSCLC by miR-153-3p/BTBD7 axis, providing a potential target for the treatment of NSCLC.