Circ_0004771 Accelerates Cell Carcinogenic Phenotypes via Suppressing miR-1253-Mediated DDAHI Inhibition in Breast Cancer

Background: 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 (R) methods, and qualified using Nanosight (TM) 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 upregulate 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.

Automated summary

Circ_0004771 accelerates cell carcinogenic phenotypes in breast cancer by upregulating DDAH1 expression through absorbing miR-1253. Additionally, circ_0004771 was found to be packaged into exosomes isolated from the serum of breast cancer patients. These findings suggest a promising molecular target for breast cancer treatment.