CircRNA circ_0008037 facilitates tumor growth and the Warburg effect via upregulating NUCKS1 by binding to miR-433-3p in non-small cell lung cancer

CircRNA circ_0008037 通过与非小细胞肺癌中的 miR-433-3p 结合上调 NUCKS1 来促进肿瘤生长和瓦堡效应

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作者:Jia Yu, Haining Zhang, Chunsheng Zhao, Guanghui Li, Yingying Zhang, Yang Sun

Background

Circular RNAs (circRNAs) participate in the genesis and progression of tumors, including non-small cell lung cancer (NSCLC). At present, the role and regulatory mechanisms of circRNAs in NSCLC have not been fully elucidated. The

Conclusion

Circ_0008037 accelerated tumor growth and elevated the Warburg effect via regulating NUCKS1 expression by adsorbing miR-433-3p, providing an underlying target for NSCLC treatment.

Methods

Expression of circ_0008037 in NSCLC tissues and cells was detected by quantitative real-time polymerase chain reaction (RT-qPCR). Loss-of-function experiments were performed to analyze the influence of circ_0008037 knockdown on proliferation, migration, invasion, and the Warburg effect of NSCLC cells. Western blotting was utilized for protein analysis. The regulatory mechanism of circ_0008037 was surveyed by bioinformatics analysis, RNA pulldown assay, and dual-luciferase reporter assay. Xenograft assay was used to validate the oncogenicity of circ_0008037 in NSCLC in vivo.

Results

Circ_0008037 was upregulated in NSCLC tissues and cells. Circ_0008037 downregulation reduced tumor growth in vivo and repressed proliferation, migration, invasion, and decreased the Warburg effect of NSCLC cells in vitro. Mechanically, circ_0008037 regulated nuclear ubiquitous casein kinase and cyclin-dependent kinase substrate 1 (NUCKS1) expression via sponging miR-433-3p. Furthermore, MiR-433-3p inhibitor reversed the inhibiting influence of circ_0008037 silencing on proliferation, migration, invasion, and the Warburg effect of NSCLC cells. Also, NUCKS1 elevation overturned the repressive influence of miR-433-3p mimic on proliferation, migration, invasion, and the Warburg effect of NSCLC cells.

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