Hsa_circ_0000520 overexpression increases CDK2 expression via miR-1296 to facilitate cervical cancer cell proliferation

• Published in: Journal of translational medicine Vol. 19; no. 1; pp. 1 - 314
• Main Authors: Zheng, Qingling, Zhang, Jin, Zhang, Ting, Liu, Yanxiang, Du, Xiuluan, Dai, Xin, Gu, Donghua
• Format: Journal Article
• Language: English
• Published: London BioMed Central Ltd 20.07.2021; BioMed Central; BMC
• Subjects: Antibodies; Apoptosis; Argonaute 2 protein; Binding sites; Cell cycle; Cell proliferation; Cervical cancer; Cervix; Circular RNA; Cyclin-dependent kinase 2; Cyclin-dependent kinases; Development and progression; Flow cytometry; Fluorescence in situ hybridization; Fluorides; Gene expression; Genetic aspects; Health aspects; hsa_circ_0000520; Hybridization; Kinases; Localization; Medical prognosis; microRNA-1296; miRNA; Physiological aspects; Protein kinases; Proteins; Ribonuclease; RNA; Tumor cell lines; China; United States > US; Japan
• ISSN: 1479-5876; 1479-5876
• DOI: 10.1186/s12967-021-02953-9

Abstract Background Circular RNA (circRNA) has been demonstrated to participate in cervical cancer development. In this study, we analyzed the role of hsa_circ_0000520 in cervical cancer. Methods Fifty-two pairs of cervical cancer and adjacent normal tissue samples were collected, and five human cervical cancer cell lines were obtained followed by the detection of hsa_circ_0000520 expression. Nuclear-cytoplasmic isolation and fluorescence in situ hybridization were performed to analyze the subcellular localization of hsa_circ_0000520 while linear RNA was digested by RNase R. Gain- or loss-of function experiments on hsa_circ_0000520 were performed, followed by detection of cell proliferation and cell cycle by EdU, Cell Counting Kit-8, colony formation assay, and flow cytometry respectively. Results Hsa_circ_0000520 and cyclin-dependent kinase 2 (CDK2) were highly expressed in cervical cancer tissues. Binding sites between microRNA-1296 (miR-1296) and hsa_circ_0000520 or CDK2 were verified. Antibody to Argonaute 2 (Ago2) could precipitate hsa_circ_0000520, indicating that hsa_circ_0000520 could competitively bind to miR-1296 via Ago2. Silencing hsa_circ_0000520 inhibited cervical cancer cell proliferation and promoted the inhibitory effects of miR-1296 on CDK2, thereby blocking cell cycle progression and promoting apoptosis. Conclusion These results support the premise that targeting hsa_circ_0000520 can be a potential approach to combat cervical cancer.