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

Abstract

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 aim of this study was to explore the role and regulatory mechanism of circRNA hsa_circ_0008037 (circ_0008037) in NSCLC. 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. 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. K E Y W O R D S circ_0008037, miR-433-3p, NSCLC, NUCKS1 † Jia Yu and Haining Zhang contribute to this work equally as co-first authors.

Circular RNA circATP9A promotes non-small cell lung cancer progression by interacting with HuR and by promoting extracellular vesicles-mediated macrophage M2 polarization

“…In NSCLC, Zhao et al noticed that NUCKS1 can promote NSCLC proliferation, invasion and migration through upregulating CDK1 expression [ 43 ]. Yu et al demonstrated that circRNA circ_0008037 promotes tumor growth and the Warburg effect by upregulating NUCKS1 through binding to miR-433-3p in NSCLC [ 44 ]. Our investigation demonstrates that circATP9A associates with HuR, thereby enhancing its expression, which in turn results in increased regulation of NUCKS1 mRNA.…”

A novel molecular mechanism mediated by circCCDC134 regulates non‐small cell lung cancer progression

“…CircRNA has been identified to be a potential target for many cancers, including NSCLC. 19,20 Here, we investigated the role of circCCDC134, a highly expressed circRNA, in the NSCLC malignant phenotype. Our results revealed that circCCDC134 knockdown inhibited NSCLC cell growth, metastasis and glycolysis, and could effectively reduce NSCLC tumor growth.…”

“…Therefore, it is necessary to continue to reveal more effective molecular targets to provide ideas for targeted therapy of NSCLC. CircRNA has been identified to be a potential target for many cancers, including NSCLC 19,20 . Here, we investigated the role of circCCDC134, a highly expressed circRNA, in the NSCLC malignant phenotype.…”