Hsa_circ_0000520 Overexpression Increases CDK2 Expression Via MiR-1296 to Facilitate Cervical Cancer Cell Proliferation

Overview

Journal J Transl Med

Publisher Biomed Central

Specialties Biomedical Engineering
General Medicine

Date 2021 Jul 21

PMID 34284793

Citations 10

Authors

Qingling Zheng

Jin Zhang

Ting Zhang

Yanxiang Liu

Xiuluan Du

Xin Dai

DongHua Gu

Affiliations

Soon will be listed here.

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.

Citing Articles

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References

Yu D, Li Y, Ming Z, Wang H, Dong Z, Qiu L . Comprehensive circular RNA expression profile in radiation-treated HeLa cells and analysis of radioresistance-related circRNAs. PeerJ. 2018; 6:e5011. PMC: 6005163. DOI: 10.7717/peerj.5011. View

Majid S, Dar A, Saini S, Chen Y, Shahryari V, Liu J . Regulation of minichromosome maintenance gene family by microRNA-1296 and genistein in prostate cancer. Cancer Res. 2010; 70(7):2809-18. DOI: 10.1158/0008-5472.CAN-09-4176. View

Kristensen L, Hansen T, Veno M, Kjems J . Circular RNAs in cancer: opportunities and challenges in the field. Oncogene. 2017; 37(5):555-565. PMC: 5799710. DOI: 10.1038/onc.2017.361. View

Zhong Y, Du Y, Yang X, Mo Y, Fan C, Xiong F . Circular RNAs function as ceRNAs to regulate and control human cancer progression. Mol Cancer. 2018; 17(1):79. PMC: 5889847. DOI: 10.1186/s12943-018-0827-8. View

Qian W, Huang T, Feng W . Circular RNA HIPK3 Promotes EMT of Cervical Cancer Through Sponging miR-338-3p to Up-Regulate HIF-1α. Cancer Manag Res. 2020; 12:177-187. PMC: 6957911. DOI: 10.2147/CMAR.S232235. View

Huang L, Qiao L, Zhu H, Jiang L, Yin L . Genomics of neonatal sepsis: has-miR-150 targeting BCL11B functions in disease progression. Ital J Pediatr. 2018; 44(1):145. PMC: 6267077. DOI: 10.1186/s13052-018-0575-9. View

Ma H, Yao Y, Yu J, Chen X, Li H . Extensive profiling of circular RNAs and the potential regulatory role of circRNA-000284 in cell proliferation and invasion of cervical cancer via sponging miR-506. Am J Transl Res. 2018; 10(2):592-604. PMC: 5835825. View

Lei X, Fang Z . GBDTCDA: Predicting circRNA-disease Associations Based on Gradient Boosting Decision Tree with Multiple Biological Data Fusion. Int J Biol Sci. 2019; 15(13):2911-2924. PMC: 6909967. DOI: 10.7150/ijbs.33806. View

Sun H, Tang W, Rong D, Jin H, Fu K, Zhang W . Hsa_circ_0000520, a potential new circular RNA biomarker, is involved in gastric carcinoma. Cancer Biomark. 2017; 21(2):299-306. DOI: 10.3233/CBM-170379. View

10.

Bai H, Yin H . Engeletin suppresses cervical carcinogenesis in vitro and in vivo by reducing NF-κB-dependent signaling. Biochem Biophys Res Commun. 2020; 526(2):497-504. DOI: 10.1016/j.bbrc.2020.03.091. View

11.

Bachmayr-Heyda A, Reiner A, Auer K, Sukhbaatar N, Aust S, Bachleitner-Hofmann T . Correlation of circular RNA abundance with proliferation--exemplified with colorectal and ovarian cancer, idiopathic lung fibrosis, and normal human tissues. Sci Rep. 2015; 5:8057. PMC: 4306919. DOI: 10.1038/srep08057. View

12.

Ou R, Mo L, Tang H, Leng S, Zhu H, Zhao L . circRNA-AKT1 Sequesters miR-942-5p to Upregulate AKT1 and Promote Cervical Cancer Progression. Mol Ther Nucleic Acids. 2020; 20:308-322. PMC: 7078494. DOI: 10.1016/j.omtn.2020.01.003. View

13.

Vu M, Yu J, Awolude O, Chuang L . Cervical cancer worldwide. Curr Probl Cancer. 2018; 42(5):457-465. DOI: 10.1016/j.currproblcancer.2018.06.003. View

14.

Ma H, Tian T, Liu X, Xia M, Chen C, Mai L . Upregulated circ_0005576 facilitates cervical cancer progression via the miR-153/KIF20A axis. Biomed Pharmacother. 2019; 118:109311. DOI: 10.1016/j.biopha.2019.109311. View

15.

Fang J, Zhang H, Jin S . Epigenetics and cervical cancer: from pathogenesis to therapy. Tumour Biol. 2014; 35(6):5083-93. DOI: 10.1007/s13277-014-1737-z. View

16.

Ruan Y, Li Z, Shen Y, Li T, Zhang H, Guo J . Functions of circular RNAs and their potential applications in gastric cancer. Expert Rev Gastroenterol Hepatol. 2020; 14(2):85-92. DOI: 10.1080/17474124.2020.1715211. View

17.

Wong S, Chan J, Lee K, Hsiao W . Differential expression of p16/p21/p27 and cyclin D1/D3, and their relationships to cell proliferation, apoptosis, and tumour progression in invasive ductal carcinoma of the breast. J Pathol. 2001; 194(1):35-42. DOI: 10.1002/path.838. View

18.

Xu Y, Yu H, Liu G . Hsa_circ_0031288/hsa-miR-139-3p/Bcl-6 regulatory feedback circuit influences the invasion and migration of cervical cancer HeLa cells. J Cell Biochem. 2020; 121(10):4251-4260. DOI: 10.1002/jcb.29650. View

19.

Yirong C, Shengchen W, Jiaxin S, Shuting W, Ziwei Z . DEHP induces neutrophil extracellular traps formation and apoptosis in carp isolated from carp blood via promotion of ROS burst and autophagy. Environ Pollut. 2020; 262:114295. DOI: 10.1016/j.envpol.2020.114295. View

20.

Liu Z, He W, Gao J, Luo J, Huang X, Gao C . Computational prediction and experimental validation of a novel synthesized pan-PIM inhibitor PI003 and its apoptosis-inducing mechanisms in cervical cancer. Oncotarget. 2015; 6(10):8019-35. PMC: 4480732. DOI: 10.18632/oncotarget.3139. View