Abstract

BackgroundThe incidence and death rate of non-small cell lung cancer (NSCLC) in China ranks the first among the malignant tumors. Circular RNA (circRNA) was reported to be involved in the progression of NSCLC. Our study aimed to investigate the underlying mechanism of circ_0020123 in NSCLC progression.MethodsQuantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of circ_0020123, miR-590-5p and Thrombospondin 2 (THBS2) in NSCLC tissues and cells. Cell proliferation and migration were examined by Cell Counting Kit-8 (CCK-8) assay and Transwell assay, respectively. Flow cytometry assay was used to detect the apoptosis of NSCLC cells. The protein levels of Ki-67, matrix metalloprotein-9 (MMP-9), Cleaved-caspase9 (Cleaved-casp9) and THBS2 were detected by Western blot. The targets of circ_0020123 and miR-590-5p were predicted by starBase 3.0 and TargetScan, and then confirmed by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. The animal experiment showed the effect of circ_0020123 on tumor growth in vivo.ResultsThe expression of circ_0020123 was upregulated in NSCLC tissues and cells. Functionally, circ_0020123 downregulation inhibited the proliferation and migration and promoted the apoptosis of NSCLC cells. Interestingly, circ_0020123 directly targeted miR-590-5p, and inhibition of miR-590-5p reversed the knockdown effects of circ_0020123 on NSCLC cells. More importantly, THBS2 was a target of miR-590-5p, and THBS2 overexpression reversed the effects of circ_0020123 knockdown on cell proliferation, migration and apoptosis in NSCLC cells. Finally, suppression of circ_0020123 inhibited tumor growth in vivo through miR-590-5p/THBS2 axis.ConclusionCircular RNA circ_0020123 regulated THBS2 by sponging miR-590-5p to promote cell proliferation and migration and inhibit cell apoptosis in NSCLC cells.

Highlights

  • The incidence and death rate of non-small cell lung cancer (NSCLC) in China ranks the first among the malignant tumors

  • Thrombospondin 2 (THBS2) acted as a target of miR-590-5p, and overexpression of THBS2 reversed the effects of circ_0020123 knockdown on NSCLC progression

  • Circ_0020123 was upregulated in NSCLC tissues and cells To begin with, Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of circ_0020123, the result showed that circ_0020123 was significantly upregulated in NSCLC tissues compared with the adjacent healthy tissues (Fig. 1a)

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Summary

Introduction

The incidence and death rate of non-small cell lung cancer (NSCLC) in China ranks the first among the malignant tumors. Circular RNA (circRNA) was reported to be involved in the progression of NSCLC. A previous report suggested that circ_0020123 acted as an oncogene in NSCLC, and circ_0020123 regulated zincfinger-enhancer binding protein 1 (ZEB1) and enhancer of zeste homolog 2 (EZH2) by competitively binding with miR-144 to induce cell progression and migration [13]. These reports suggested that circ_0020123 was a vital factor in the pathogenesis of NSCLC, and its function and molecular mechanism need to be further studied

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