Circ_0074027 Contributes to Non-Small Cell Lung Cancer Progression by Upregulating CUL4B Expression Through miR-335-5p

Autor: Maofen Jiang, Kaizhong Yu, Chaoqun Yu, Weiyu Shen, Jianjian Ying
Rok vydání: 2022
Předmět:
Zdroj: Cancer Biotherapy and Radiopharmaceuticals. 37:73-83
ISSN: 1557-8852
1084-9785
DOI: 10.1089/cbr.2020.3579
Popis: Background: Circular RNAs (circRNAs) are crucial regulators in human cancers, including nonsmall cell lung cancer (NSCLC). In this study, we aim to explore the biological functions and molecular mechanisms of circ_0074027 in NSCLC. Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to determine the expression of circ_0074027, paired like homeodomain 1 (PITX1) mRNA, microRNA-335-5p (miR-335-5p), and cullin 4B (CUL4B) mRNA. The feature of circ_0074027 was analyzed by RNase R digestion assay. Flow cytometry analysis was adopted to analyze cell cycle and cell apoptosis. Cell counting kit-8 (CCK-8) assay and colony formation assay were performed to assess cell proliferation. Western blot assay was conducted to measure protein levels. Dual-luciferase reporter and RNA pull-down assays were carried out to verify the relationships among circ_0074027, miR-335-5p, and CUL4B. The murine xenograft model was established to investigate the role of circ_0074027 in vivo. Results: High expression of circ_0074027 was found in NSCLC tissues and cells. Circ_0074027 knockdown suppressed cell viability, cell cycle process, and colony formation and promoted apoptosis in NSCLC cells in vitro and inhibited tumor growth in vivo. Circ_0074027 acted as a sponge of miR-335-5p. The effect of circ_0074027 knockdown on NSCLC progression was weakened by miR-335-5p inhibition. Moreover, CUL4B was a target gene of miR-335-5p. CUL4B overexpression reversed the inhibitory effects on cell viability, cell cycle process, and colony formation and the promotional effect on cell apoptosis caused by miR-335-5p in NSCLC. Conclusion: Circ_0074027 facilitated NSCLC cell progression through regulating miR-335-5p/CUL4B axis.
Databáze: OpenAIRE