Knockdown of circ‐RAD23B inhibits non‐small cell lung cancer progression via the miR‐142‐3p/MAP4K3 axis

Autor: Qingyang Zhuang, Zhangzhou Huang, Wu Zhuang, Yaping Hong, Yunjian Huang
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Thoracic Cancer, Vol 13, Iss 5, Pp 750-760 (2022)
Druh dokumentu: article
ISSN: 1759-7714
1759-7706
61354333
DOI: 10.1111/1759-7714.14319
Popis: Abstract Background The development of non‐small cell lung cancer (NSCLC) is associated with the deregulation of circRNAs. The objective of this study was to investigate the effects of circ‐RAD23B in NSCLC. Methods Circ‐RAD23B expression, miR‐142‐3p and MAP4K3 was detected by qPCR. Cell proliferation was investigated by CCK‐8 assay and colony formation assay. Cell migration and invasion were assessed by transwell assay. Angiogenesis ability was assessed by tube formation assay. Cell cycle distribution and cell apoptosis were monitored by flow cytometry. The predicted binding relationship between miR‐142‐3p and circ‐RAD23B or MAP4K3 was verified by dual‐luciferase reporter assay. The protein level of MAP4K3 was detected by western blot. Animal models were established to determine the role of circ‐RAD23B in vivo. Results Circ‐RAD23B was shown to be upregulated in NSCLC tissues and cells. Knockdown of circ‐RAD23B inhibited proliferation, migration, invasion, angiogenesis and promoted cell cycle arrest and apoptosis in NSCLC cells, and circ‐RAD23B knockdown also impeded tumor growth in vivo. Circ‐RAD23B acted as miR‐142‐3p sponge to inhibit miR‐142‐3p expression and thus enrich the expression of MAP4K3, a target of miR‐142‐3p. Rescue experiments presented that miR‐142‐3p inhibition reversed the effects of circ‐RAD23B knockdown, and MAP4K3 overexpression abolished the effects of miR‐142‐3p restoration. In addition, we found that circ‐RAD23B knockdown led to decreased phosphorylation expression of ERK1/2, JNK and p38, three key groups of the MAPK signaling pathway. Conclusions Circ‐RAD23B knockdown inhibited NSCLC development by regulating the miR‐142‐3p/MAP4K3 axis, which might be associated with the inactivation of the MAPK signaling pathway.
Databáze: Directory of Open Access Journals
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