CircRNA8924 Promotes Cervical Cancer Cell Proliferation, Migration and Invasion by Competitively Binding to MiR-518d-5p /519-5p Family and Modulating the Expression of CBX8

被引:83
作者
Liu, Jiamei [1 ]
Wang, Danbo [1 ]
Long, Zaiqiu [1 ]
Liu, Jing [1 ]
Li, Weishan [1 ]
机构
[1] China Med Univ, Canc Hosp, Dept Gynecol, Liaoning Canc Hosp & Inst, 44 Xiaoheyan Rd, Shenyang 110042, Liaoning, Peoples R China
关键词
Cervical cancer; CircRNA; CeRNA; MiRNA family; CircRNA8924; MiR-518d-5p/519-5p; CBX8; CIRCULAR RNA; PROFILE; IDENTIFICATION; STATISTICS; CYCLE;
D O I
10.1159/000491716
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Background/Aims: Circular RNAs (circRNAs) play a significant role in the development and progression of various human cancers. However, the expression and function of circRNAs in cervical cancer (CC) have rarely been explored. The aim of this study was to investigate the biological function of circRNA8924 in CC and elucidate the possible molecular mechanism involved. Methods: Quantitative polymerase chain reaction was used to determine mRNA expression of circRNA8924, miR-518d-5p/519-5p and CBX8 in CC tissues and cells. CBX8 protein expression was measured by Western blotting. The CCK-8 assay was used to evaluate cell proliferation, and the transwell assay to determine cell migration and invasion. The luciferase reporter assay was used to determine the direct regulation of miR-518d-5p/519-5p and circRNA8924 or CBX8 Results: The study demonstrated that the expression level of circRNA8924 in CC was significantly higher than that in the adjacent normal tissues (P < 0.001), and that it was also associated with tumor size, FIGO staging and myometrial invasion. The knockdown of circRNA8924 significantly inhibited the proliferation, migration and invasion of CC cells SiHa and HeLa. The expression level of miR-518d-5p/519-5p was negatively correlated with circRNA8924, and circRNA8924 regulated CBX8 by competitively binding to miR-518d-5p/519-5p. Conclusions: CircRNA8924 is highly expressed in CC tissue and can be considered a competitive endogenous RNA of the miR-518d-5p/519-5p family to promote the malignant biological behavior of CC cells. It is suggested that it may serve as a new biomarker for CC diagnosis and disease progression and provide potential targets for targeted therapy. (C) 2018 The Author(s) Published by S Karger AG, Basel
引用
收藏
页码:173 / 184
页数:12
相关论文
共 42 条
[1]  
[Anonymous], J PATHOL
[2]   Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project [J].
Birney, Ewan ;
Stamatoyannopoulos, John A. ;
Dutta, Anindya ;
Guigo, Roderic ;
Gingeras, Thomas R. ;
Margulies, Elliott H. ;
Weng, Zhiping ;
Snyder, Michael ;
Dermitzakis, Emmanouil T. ;
Stamatoyannopoulos, John A. ;
Thurman, Robert E. ;
Kuehn, Michael S. ;
Taylor, Christopher M. ;
Neph, Shane ;
Koch, Christoph M. ;
Asthana, Saurabh ;
Malhotra, Ankit ;
Adzhubei, Ivan ;
Greenbaum, Jason A. ;
Andrews, Robert M. ;
Flicek, Paul ;
Boyle, Patrick J. ;
Cao, Hua ;
Carter, Nigel P. ;
Clelland, Gayle K. ;
Davis, Sean ;
Day, Nathan ;
Dhami, Pawandeep ;
Dillon, Shane C. ;
Dorschner, Michael O. ;
Fiegler, Heike ;
Giresi, Paul G. ;
Goldy, Jeff ;
Hawrylycz, Michael ;
Haydock, Andrew ;
Humbert, Richard ;
James, Keith D. ;
Johnson, Brett E. ;
Johnson, Ericka M. ;
Frum, Tristan T. ;
Rosenzweig, Elizabeth R. ;
Karnani, Neerja ;
Lee, Kirsten ;
Lefebvre, Gregory C. ;
Navas, Patrick A. ;
Neri, Fidencio ;
Parker, Stephen C. J. ;
Sabo, Peter J. ;
Sandstrom, Richard ;
Shafer, Anthony .
NATURE, 2007, 447 (7146) :799-816
[3]   Regulation of circRNA biogenesis [J].
Chen, Ling-Ling ;
Yang, Li .
RNA BIOLOGY, 2015, 12 (04) :381-388
[4]   Using circular RNA hsa_circ_0000190 as a new biomarker in the diagnosis of gastric cancer [J].
Chen, Shijun ;
Li, Tianwen ;
Zhao, Qianfu ;
Xiao, Bingxiu ;
Guo, Junming .
CLINICA CHIMICA ACTA, 2017, 466 :167-171
[5]   Cancer Statistics in China, 2015 [J].
Chen, Wanqing ;
Zheng, Rongshou ;
Baade, Peter D. ;
Zhang, Siwei ;
Zeng, Hongmei ;
Bray, Freddie ;
Jemal, Ahmedin ;
Yu, Xue Qin ;
He, Jie .
CA-A CANCER JOURNAL FOR CLINICIANS, 2016, 66 (02) :115-132
[6]  
Cortes-Lopez Mariela, 2016, Yale Journal of Biology and Medicine, V89, P527
[7]   Circular RNAs in cancer: an emerging key player [J].
Dong, Yeping ;
He, Dan ;
Peng, Zhenzi ;
Peng, Wei ;
Shi, Wenwen ;
Wang, Jun ;
Li, Bin ;
Zhang, Chunfang ;
Duan, Chaojun .
JOURNAL OF HEMATOLOGY & ONCOLOGY, 2017, 10 :1-8
[8]   Molecular biology of human papillomavirus infection and cervical cancer [J].
Doorbar, John .
CLINICAL SCIENCE, 2006, 110 (05) :525-541
[9]   Foxo3 circular RNA retards cell cycle progression via forming ternary complexes with p21 and CDK2 [J].
Du, William W. ;
Yang, Weining ;
Liu, Elizabeth ;
Yang, Zhenguo ;
Dhaliwal, Preet ;
Yang, Burton B. .
NUCLEIC ACIDS RESEARCH, 2016, 44 (06) :2846-2858
[10]   Stable X chromosome inactivation involves the PRC1 Polycomb complex and requires histone MACROH2A1 and the CULLIN3/SPOP ubiquitin E3 ligase [J].
Hernádez-Muñoz, I ;
Lund, AH ;
van der Stoop, P ;
Boutsma, E ;
Muijrers, I ;
Verhoeven, E ;
Nusinow, DA ;
Panning, B ;
Marahrens, Y ;
van Lohuizen, M .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (21) :7635-7640