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Circ_0081723 enhances cervical cancer progression and modulates CREBRF via sponging miR-545-3p
Qiongyan Ma1, Weiwei Yu2, Zhaobin Li3
1Department of Gynaecology and Obstetrics, Gongli Hospital of Shanghai Pudong New Area, Shanghai, China.
Abstract:
Circular RNAs (circRNAs) have been confirmed to be an important modulator and therapeutic target of cervical cancer (CC). The aim of this study is to explore the role and mechanism of circ_0081723 in CC progression. Circ_0081723, microRNA-545-3p (miR-545-3p), and CREB3 regulatory factor (CREBRF) levels were detected using quantitative real-time PCR (qRT-PCR) assay. CREBRF, ki-67, Bcl-2 related X protein (Bax), and E-cadherin expression levels were determined using western blot (WB) and immunohistochemistry (IHC) assays. Cell proliferation was assessed using Cell Counting Kit-8 (CCK-8), cell colony formation, and 5-ethynyl-2'-deoxyuridine (EdU) assays. Flow cytometry was used to measure cell apoptosis. Cell migration and invasion were examined using Transwell assay. Interaction between miR-545-3p and circ_0081723 or CREBRF was verified using dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assays. The biological role of circ_0081723 on CC growth was examined using the xenograft tumor model in vivo. Circ_0081723 and CREBRF were increased, and miR-545-3p was decreased in CC tissues and cells. Circ_0081723 silencing suppressed CC cell growth and motility whereas boosted CC cell apoptosis. Besides, circ_0081723 acted as a molecular sponge for miR-545-3p, and circ_0081723 knockdown-induced effects were largely reversed by miR-545-3p downregulation in CC cells. Moreover, miR-545-3p repressed CC progression by targeting CREBRF. Circ_0081723 absence blocked xenograft tumor growth in vivo. Circ_0081723 stimulated CC cell malignant behaviors by regulating the miR-545-3p/CREBRF pathway, providing a possible circRNA-targeted therapy for CC.
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