Downregulation of circATXN7 represses non‐small cell lung cancer growth by releasing miR‐7‐5p. Issue 11 (21st April 2022)

• Record Type: Journal Article
• Authors: Li, Dongliang; Fu, Zejun; Dong, Chaoqun; Song, Yongming
• Is Part Of: Thoracic cancer. Volume 13:Issue 11(2022)
• Page Start: 1597
• Page End: 1610
• Publication Date: 2022-04-21
• Subjects: circATXN7 -- miR‐7‐5p -- NSCLC -- PFN2; Chest -- Cancer -- Periodicals; Chest -- Cancer -- Treatment -- Periodicals; Chest -- Surgery -- Periodicals; 616.99494005
• DOI: 10.1111/1759-7714.14426
• Languages: English
• ISSNs: 1759-7706

Abstract

Abstract: Background: Circular RNAs (circRNAs) participate in the occurrence and progression of many cancers. CircRNA ataxin 7 (circATXN7) (circBase ID: hsa_circ_0066436) plays a promoting influence on gastric cancer progression. However, the biological role of circATXN7 in non‐small cell lung cancer (NSCLC) is indistinct. Methods: Levels of circATXN7, microRNA (miR)‐7‐5p, and profilin 2 (PFN2) mRNA were detected using quantitative real‐time polymerase chain reaction (RT‐qPCR). Proliferation, apoptosis, metastasis, and invasion were analyzed using cell counting kit‐8 (CCK‐8), colony formation, 5‐ethynyl‐2′‐deoxyuridine (EdU), flow cytometry, and transwell assays. Protein levels were analyzed using western blotting (WB) and immunohistochemistry (IHC). The relationship between circATXN7 or PFN2 and miR‐7‐5p was analyzed by dual‐luciferase reporter and RNA immunoprecipitation (RIP) assays. The biological function of circATXN7 was verified by xenograft assay. Results: CircATXN7 and PFN2 were highly expressed in NSCLC, whereas miR‐7‐5p expression had the opposite trend. CircATXN7 overexpression constrained apoptosis and promoted proliferation, metastasis, invasion, and epithelial‐mesenchymal transition of NSCLC cells, but circATXN7 silencing played the opposing influence and repressed xenograft tumor growth in vivo. CircATXN7 served as a miR‐7‐5p sponge, and circATXN7 regulated malignant behaviors of NSCLC cells through sponging miR‐7‐5p. PFN2 acted as a miR‐7‐5p target. PFN2 silencing overturned the promoting effect of miR‐7‐5p inhibitor on NSCLC cell malignancy, while PFN2 overexpression reversed the inhibitory impact of miR‐7‐5p mimic on NSCLC cell malignancy. Conclusion: CircATXN7 accelerated the malignancy of NSCLC cells through adsorbing miR‐7‐5p and upregulating PFN2, offering evidence to support circATXN7 as a target for NSCLC treatment. Abstract : Graphic illustrating that circATXN7 adsorbs miR‐7‐5p and sequesters miR‐7‐5p activity, and subsequently relieves the inhibitory effect of miR‐7‐5p on PFN2, leading to the promotion of NSCLC progression.