Cancer Management and Research (Jan 2021)
Circ_0004771 Accelerates Cell Carcinogenic Phenotypes via Suppressing miR-1253-Mediated DDAH1 Inhibition in Breast Cancer
Abstract
Xubei Ding,1,* Junjun Zheng,2,* Mingxiang Cao3 1Thyroid and Breast Surgery, Jingmen No.1 People’s Hospital, Jingmen, Hubei, People’s Republic of China; 2Pharmacy Intravenous Admixture Services, Jingmen No.2 People’s Hospital, Jingmen, Hubei, People’s Republic of China; 3Department of Anesthesiology, Jingmen No.1 People’s Hospital, Jingmen, Hubei, People’s Republic of China*These authors contributed equally to this workCorrespondence: Mingxiang CaoDepartment of Anesthesiology, Jingmen No.1 People’s Hospital, No. 168, Xiangshan Street, Jingmen, Hubei 448000, People’s Republic of ChinaEmail [email protected]: Circ_0004771 was demonstrated to mediate cell growth promotion and apoptosis suppression in breast cancer (BC). Herein, the precise functions and mechanism of circ_0004771 in the biological property of BC cells were investigated.Methods: The expression of circ_0004771, microRNA (miR)-1253 and dimethylarginine dimethylaminohydrolase 1 (DDAH1) mRNA was analyzed using quantitative real-time polymerase chain reaction. The proliferation, apoptosis, migration, invasion, adhesion, Western blot and in vivo tumorigenesis assays were employed to evaluate the roles of circ_0004771 and DDAH1 in BC tumorigenesis. The interaction between miR-1253 and circ_0004771 or DDAH1 was validated by dual-luciferase reporter, pull-down and RNA immunoprecipitation (RIP) assay. Exosomes were isolated by Exoquick-TC® methods, and qualified using Nanosight™ technology and Western blot.Results: Circ_0004771 or DDAH1 expression was elevated in BC, and silencing either of them suppressed cell malignant phenotypes, thus impeding BC progression. Importantly, circ_0004771 up-regulation attenuated the anticancer action of DDAH1-knockdown in BC. Additionally, we confirmed that circ_0004771 functioned as a sponge of miR-1253 to up-regulate DDAH1 expression. Moreover, xenograft assay exhibited that circ_0004771 knockdown also hindered tumor growth in vivo via regulating DDAH1 and miR-1253. Besides that, it was found that circ_0004771 was packaged into exosomes isolated from the serum of BC.Conclusion: Circ_0004771 accelerated cell carcinogenic phenotypes via up-regulating DDAH1 expression through absorbing miR-1253 in BC. Besides, circ_0004771 was packaged into exosomes isolated from the serum of BC. All these findings suggested a promising molecular target for BC treatment.Keywords: circ_0004771, miR-1253, DDAH1, breast cancer, exosome
