Downregulation of circ<scp>ATXN7</scp> represses non‐small cell lung cancer growth by releasing mi<scp>R</scp>‐7‐5p
Dongliang Li, Zejun Fu, Chaoqun Dong, Yongming Song
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.