Cancer Management and Research (May 2021)
Circ_0001944 Contributes to Glycolysis and Tumor Growth by Upregulating NFAT5 Through Acting as a Decoy for miR-142-5p in Non-Small Cell Lung Cancer
Abstract
Yawei Dou,1 Wei Tian,1 Hongtao Wang,1 Shanshan Lv2 1Department of Thoracic Surgery, Shaanxi Province People’s Hospital, Xi’an, 710068, People’s Republic of China; 2Department of Cardiovascular Surgery, Xijing Hospital of Airforce Medical University, Xi’an, 710032, People’s Republic of ChinaCorrespondence: Shanshan LvDepartment of Cardiovascular Surgery, Xijing Hospital of Airforce Medical University, No. 169, Changle West Road, Xi’an, 710032, People’s Republic of ChinaTel +86-29-84775313Email [email protected]: Circular RNAs (circRNAs) participate in the tumorigenesis of various cancers. CircRNA hsa_circ_0001944 (circ_0001944), derived from the TCONS_l2_00030860 gene, has been uncovered to be upregulated in NSCLC (non-small cell lung cancer). Nevertheless, the influence of circ_0001944 on glycolysis and tumor growth in NSCLC is unclear.Methods: Expression trend of circ_0001944 in NSCLC tissues and cells were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). Loss-of-function experiments were performed to assess the influence of circ_0001944 knockdown on proliferation, migration, invasion, and glycolysis of NSCLC cells. Protein levels were assessed by Western blotting. The regulatory mechanism of circ_0001944 was analyzed by bioinformatics analysis, dual-luciferase reporter assay, and/or RNA pull-down assay. The tumorigenicity of circ_0001944 was confirmed by xenograft assay.Results: Circ_0001944 was highly expressed in NSCLC, and NSCLC patients with high expression of circ_0001944 had a worse prognosis. Circ_0001944 silencing decreased xenograft tumor growth in vivo and repressed proliferation, migration, invasion, and glycolysis of NSCLC cells in vitro. Circ_0001944 was verified as a decoy for microRNA (miR)-142-5p, which targeted NFAT5 (nuclear factor of activated T cells 5). MiR-142-5p was downregulated while NFAT5 was upregulated in NSCLC. Both miR-142-5p inhibition and NFAT5 overexpression offset the suppressive impact of circ_0001944 silencing on proliferation, migration, invasion, and glycolysis of NSCLC cells. Circ_0001944 adsorbed miR-142-5p to elevate NFAT5 expression in NSCLC cells.Conclusion: Circ_0001944 promotes proliferation, migration, invasion, and glycolysis of NSCLC cells by upregulating NFAT5 through adsorbing miR-142-5p, offering a novel mechanism for understanding the advancement of NSCLC.Keywords: NSCLC, circ_0001944, miR-142-5p, NFAT5, glycolysis
