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CircVAPA exerts oncogenic property in non‐small cell lung cancer by the miR‐876‐5p/WNT5A axis
Author(s) -
Zhao Yan,
Dai Qiangsheng,
Fu Xiaohong,
Chen Qianqi,
Tang Yueqiang,
Gao Xiaoping,
Zhou Qiming
Publication year - 2021
Publication title -
the journal of gene medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.689
H-Index - 91
eISSN - 1521-2254
pISSN - 1099-498X
DOI - 10.1002/jgm.3325
Subject(s) - gene knockdown , wnt signaling pathway , carcinogenesis , cancer research , gene silencing , cell growth , microrna , biology , cell , signal transduction , cell culture , chemistry , cancer , microbiology and biotechnology , gene , biochemistry , genetics
Background Non‐small cell lung cancer (NSCLC) is one of the most fatal malignant tumors. Emerging studies have clarified the crucial roles of circular RNAs (circRNAs) in the tumorigenesis of cancers. CircVAPA was demonstrated to function in some human cancers. The present study aimed to investigate the role of circVAPA in NSCLC. Methods A quantitative real‐time polymerase chain reaction was used to measure the expression of genes. Actinomycin D and RNase R were employed to examine the stability of circVAPA. Cell‐counting kit‐8, 5‐ethynyl‐2′‐deoxyuridine, Transwell and sphere formation assays, and well as western blot analysis, were conducted to examine the changes of NSCLC cells in response to circVAPA knockdown. A luciferase reporter assay was conducted for the molecular mechanism. Results Our findings demonstrated high expression of circVAPA in tissues and cell lines of NSCLC. Knockdown of circVAPA had a suppressive effect on cell proliferation, migration, invasion and stemness, and also inhibited tumor growth in vivo . Mechanistically, circVAPA acted as a competing endogenous RNA to up‐regulate WNT5A by sponging miR‐876‐5p. Moreover, circVAPA activated Wnt/β‐catenin signaling by up‐regulation of WNT5A. Rescue assays showed that silencing of miR‐876‐5p or overexpression of WNT5A reversed the circVAPA knockdown‐mediated inhibition on cellular processes in NSCLC. Conclusions CircVAPA promotes aggressive phenotypes of NSCLC cells by the miR‐876‐5p/WNT5A axis activating Wnt/β‐catenin signaling.

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