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Cancer Cell International
Published in: Cancer Cell International 1/2020

01-12-2020 | Cervical Cancer | Primary research

circ_0084927 promotes cervical carcinogenesis by sponging miR-1179 that suppresses CDK2, a cell cycle-related gene

Authors: Xinhua Qu, Liumei Zhu, Linlin Song, Shaohua Liu

Published in: Cancer Cell International | Issue 1/2020

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Abstract

Background

Cervical cancer (CC) is a malignant tumor found in the lowermost part of the womb. Evolving studies on CC have reported that circRNA plays a crucial role in CC progression. In this study, we investigated the main function of a novel circRNA, circ_0084927, and its regulatory network in CC development.

Methods

qRT-PCR was applied to evaluate the expression of circ_0084927, miR-1179, and CDK2 mRNA in CC tissues and cells. Dual-luciferase reporting experiments and RNA immunoprecipitation (RIP) assay were conducted to validate the target relationship of miR-1179 with circ_0084927 and CDK2 mRNA. CCK-8 and BrdU assays were also used to evaluate CC cell proliferation. The adhesion and apoptosis phenotypes of CC cells were measured using cell–matrix adhesion and caspase 3 activation assay. Flow cytometry was also employed to detect the CC cell cycle.

Results

Our results indicated that circ_0084927 was up-regulated in CC tissues and cells. Findings also revealed that circ_0084927 silence inhibited CC cell proliferation and adhesion while facilitating apoptosis and triggering cell cycle arrest. However, miR-1179 down-regulation appeared in CC tissues. Apart from observing that circ_0084927 abolished miR-1179’s inhibitory effects on cell proliferation and adhesion, it was found that CDK2 was up-regulated in CC tissues and was instrumental in cancer promotion. Also observed was that miR-1179 directly targeted CDK2, thereby inhibiting CDK2’s promotion on the malignant phenotypes of CC cells. Lastly, results indicated that circ_0084927 revoked the inhibitory effect of miR-1179 on CDK2 by sponging miR-1179.

Conclusion

circ_0084927 promoted cervical carcinogenesis by sequestering miR-1179, which directly targeted CDK2. Our results also provided novel candidate targets for CC treatment in that it revealed the circ_0084927/miR-1179/CDK2 regulatory network that strengthened CC aggressiveness.
Appendix
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Literature
1.
Arbyn M, Weiderpass E, Bruni L, de Sanjose S, Saraiya M, Ferlay J, Bray F. Estimates of incidence and mortality of cervical cancer in 2018: a worldwide analysis. Lancet Glob Health. 2020;8(2):e191–203.PubMedCrossRef
2.
Brisson M, Kim JJ, Canfell K, Drolet M, Gingras G, Burger EA, Martin D, Simms KT, Benard E, Boily MC, et al. Impact of HPV vaccination and cervical screening on cervical cancer elimination: a comparative modelling analysis in 78 low-income and lower-middle-income countries. Lancet. 2020;395(10224):575–90.PubMedPubMedCentralCrossRef
3.
Zapatka M, Borozan I, Brewer DS, Iskar M, Grundhoff A, Alawi M, Desai N, Sultmann H, Moch H, Pathogens P, et al. The landscape of viral associations in human cancers. Nat Genet. 2020;52(3):320–30.PubMedCrossRefPubMedCentral
4.
Wang R, Pan W, Jin L, Huang W, Li Y, Wu D, Gao C, Ma D, Liao S. Human papillomavirus vaccine against cervical cancer: opportunity and challenge. Cancer Lett. 2020;471:88–102.PubMedCrossRef
5.
Chinn J, Tewari KS. Multimodality screening and prevention of cervical cancer in sub-Saharan Africa: a collaborative model. Curr Opin Obstet Gynecol. 2020;32(1):28–35.PubMedCrossRef
6.
7.
Lapresa M, Parma G, Portuesi R, Colombo N. Neoadjuvant chemotherapy in cervical cancer: an update. Expert Rev Anticancer Ther. 2015;15(10):1171–81.PubMedCrossRef
8.
9.
Ventriglia J, Paciolla I, Pisano C, Cecere SC, Di Napoli M, Tambaro R, Califano D, Losito S, Scognamiglio G, Setola SV, et al. Immunotherapy in ovarian, endometrial and cervical cancer: state of the art and future perspectives. Cancer Treat Rev. 2017;59:109–16.PubMedCrossRef
10.
11.
Kapranov P, Cawley SE, Drenkow J, Bekiranov S, Strausberg RL, Fodor SP, Gingeras TR. Large-scale transcriptional activity in chromosomes 21 and 22. Science. 2002;296(5569):916–9.PubMedCrossRef
12.
Hsiao KY, Lin YC, Gupta SK, Chang N, Yen L, Sun HS, Tsai SJ. Noncoding effects of circular RNA CCDC66 promote colon cancer growth and metastasis. Cancer Res. 2017;77(9):2339–50.PubMedPubMedCentralCrossRef
13.
14.
Zhang PF, Pei X, Li KS, Jin LN, Wang F, Wu J, Zhang XM. Circular RNA circFGFR1 promotes progression and anti-PD-1 resistance by sponging miR-381-3p in non-small cell lung cancer cells. Mol Cancer. 2019;18(1):179.PubMedPubMedCentralCrossRef
15.
Xue D, Wang H, Chen Y, Shen D, Lu J, Wang M, Zebibula A, Xu L, Wu H, Li G, et al. Circ-AKT3 inhibits clear cell renal cell carcinoma metastasis via altering miR-296-3p/E-cadherin signals. Mol Cancer. 2019;18(1):151.PubMedPubMedCentralCrossRef
16.
Huang X, He M, Huang S, Lin R, Zhan M, Yang D, Shen H, Xu S, Cheng W, Yu J, et al. Circular RNA circERBB2 promotes gallbladder cancer progression by regulating PA2G4-dependent rDNA transcription. Mol Cancer. 2019;18(1):166.PubMedPubMedCentralCrossRef
17.
Cai H, Zhang P, Xu M, Yan L, Liu N, Wu X. Circular RNA hsa_circ_0000263 participates in cervical cancer development by regulating target gene of miR-150-5p. J Cell Physiol. 2019;234(7):11391–400.PubMedCrossRef
18.
Tang Q, Chen Z, Zhao L, Xu H. Circular RNA hsa_circ_0000515 acts as a miR-326 sponge to promote cervical cancer progression through up-regulation of ELK1. Aging. 2019;11(22):9982–99.PubMedPubMedCentralCrossRef
19.
Shao S, Wang C, Wang S, Zhang H, Zhang Y. Hsa_circ_0075341 is up-regulated and exerts oncogenic properties by sponging miR-149-5p in cervical cancer. Biomed Pharmacother. 2020;121:109582.PubMedCrossRef
20.
Wang H, Zhao Y, Chen M, Cui J. Identification of novel long non-coding and circular RNAs in human papillomavirus-mediated cervical cancer. Front Microbiol. 2017;8:1720.PubMedPubMedCentralCrossRef
21.
Ma HB, Yao YN, Yu JJ, Chen XX, Li HF. 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.PubMedPubMedCentral
22.
Hu C, Wang Y, Li A, Zhang J, Xue F, Zhu L. Overexpressed circ_0067934 acts as an oncogene to facilitate cervical cancer progression via the miR-545/EIF3C axis. J Cell Physiol. 2019;234(6):9225–32.PubMedCrossRef
23.
Li S, Teng S, Xu J, Su G, Zhang Y, Zhao J, Zhang S, Wang H, Qin W, Lu ZJ, et al. Microarray is an efficient tool for circRNA profiling. Brief Bioinform. 2019;20(4):1420–33.PubMedCrossRef
24.
Yi Y, Liu Y, Wu W, Wu K, Zhang W. Reconstruction and analysis of circRNAmiRNAmRNA network in the pathology of cervical cancer. Oncol Rep. 2019;41(4):2209–25.PubMedPubMedCentral
25.
Wei WF, Zhou CF, Wu XG, He LN, Wu LF, Chen XJ, Yan RM, Zhong M, Yu YH, Liang L, et al. MicroRNA-221-3p, a TWIST2 target, promotes cervical cancer metastasis by directly targeting THBS2. Cell Death Dis. 2017;8(12):3220.PubMedPubMedCentralCrossRef
26.
Hou T, Ou J, Zhao X, Huang X, Huang Y, Zhang Y. MicroRNA-196a promotes cervical cancer proliferation through the regulation of FOXO1 and p27Kip1. Br J Cancer. 2014;110(5):1260–8.PubMedPubMedCentralCrossRef
27.
Chandrasekaran KS, Sathyanarayanan A, Karunagaran D. MicroRNA-214 suppresses growth, migration and invasion through a novel target, high mobility group AT-hook 1, in human cervical and colorectal cancer cells. Br J Cancer. 2016;115(6):741–51.PubMedPubMedCentralCrossRef
28.
Zhang P, Kong F, Deng X, Yu Y, Hou C, Liang T, Zhu L. MicroRNA-326 suppresses the proliferation, migration and invasion of cervical cancer cells by targeting ELK1. Oncol Lett. 2017;13(5):2949–56.PubMedPubMedCentralCrossRef
29.
Xu X, Cai N, Zhi T, Bao Z, Wang D, Liu Y, Jiang K, Fan L, Ji J, Liu N. MicroRNA-1179 inhibits glioblastoma cell proliferation and cell cycle progression via directly targeting E2F transcription factor 5. Am J Cancer Res. 2017;7(8):1680–92.PubMedPubMedCentral
30.
Li Y, Qin C. MiR-1179 inhibits the proliferation of gastric cancer cells by targeting HMGB1. Hum Cell. 2019;32(3):352–9.PubMedCrossRef
31.
Heller G, Altenberger C, Steiner I, Topakian T, Ziegler B, Tomasich E, Lang G, End-Pfutzenreuter A, Zehetmayer S, Dome B, et al. DNA methylation of microRNA-coding genes in non-small-cell lung cancer patients. J Pathol. 2018;245(4):387–98.PubMedPubMedCentralCrossRef
32.
Lin C, Hu Z, Yuan G, Su H, Zeng Y, Guo Z, Zhong F, Jiang K, He S. MicroRNA-1179 inhibits the proliferation, migration and invasion of human pancreatic cancer cells by targeting E2F5. Chem Biol Interact. 2018;291:65–71.PubMedCrossRef
33.
Li WJ, Xie XX, Bai J, Wang C, Zhao L, Jiang DQ. Increased expression of miR-1179 inhibits breast cancer cell metastasis by modulating Notch signaling pathway and correlates with favorable prognosis. Eur Rev Med Pharmacol Sci. 2018;22(23):8374–82.PubMed
34.
Saurus P, Kuusela S, Dumont V, Lehtonen E, Fogarty CL, Lassenius MI, Forsblom C, Lehto M, Saleem MA, Groop PH, et al. Cyclin-dependent kinase 2 protects podocytes from apoptosis. Sci Rep. 2016;6:21664.PubMedPubMedCentralCrossRef
35.
Bonin S, Pracella D, Barbazza R, Dotti I, Boffo S, Stanta G. PI3K/AKT signaling in breast cancer molecular subtyping and lymph node involvement. Dis Markers. 2019;2019:7832376.PubMedPubMedCentralCrossRef
36.
Abd El-Karim SS, Syam YM, El Kerdawy AM, Abdelghany TM. New thiazol-hydrazono-coumarin hybrids targeting human cervical cancer cells: synthesis, CDK2 inhibition, QSAR and molecular docking studies. Bioorg Chem. 2019;86:80–96.PubMedCrossRef
37.
Guo JM, Xiao BX, Liu Q, Zhang S, Liu DH, Gong ZH. Anticancer effect of aloe-emodin on cervical cancer cells involves G2/M arrest and induction of differentiation. Acta Pharmacol Sin. 2007;28(12):1991–5.PubMedCrossRef
38.
Choi JS, Shin S, Jin YH, Yim H, Koo KT, Chun KH, Oh YT, Lee WH, Lee SK. Cyclin-dependent protein kinase 2 activity is required for mitochondrial translocation of Bax and disruption of mitochondrial transmembrane potential during etoposide-induced apoptosis. Apoptosis. 2007;12(7):1229–41.PubMedCrossRef
39.
Wu K, Yi Y, Liu F, Wu W, Chen Y, Zhang W. Identification of key pathways and genes in the progression of cervical cancer using bioinformatics analysis. Oncol Lett. 2018;16(1):1003–9.PubMedPubMedCentral
40.
Tian RQ, Wang XH, Hou LJ, Jia WH, Yang Q, Li YX, Liu M, Li X, Tang H. MicroRNA-372 is down-regulated and targets cyclin-dependent kinase 2 (CDK2) and cyclin A1 in human cervical cancer, which may contribute to tumorigenesis. J Biol Chem. 2011;286(29):25556–63.PubMedPubMedCentralCrossRef
41.
Duan S, Wu A, Chen Z, Yang Y, Liu L, Shu Q. miR-204 regulates cell proliferation and invasion by targeting EphB2 in human cervical cancer. Oncol Res. 2018;26(5):713–23.PubMedCrossRefPubMedCentral
42.
Luthi AU, Martin SJ. The CASBAH: a searchable database of caspase substrates. Cell Death Differ. 2007;14(4):641–50.PubMedCrossRef
43.
44.
Song T, Xu A, Zhang Z, Gao F, Zhao L, Chen X, Gao J, Kong X. CircRNA hsa_circRNA_101996 increases cervical cancer proliferation and invasion through activating TPX2 expression by restraining miR-8075. J Cell Physiol. 2019;234(8):14296–305.PubMedCrossRef
45.
Wen Y, Wang Y, Xing Z, Liu Z, Hou Z. Microarray expression profile and analysis of circular RNA regulatory network in malignant pleural effusion. Cell Cycle. 2018;17(24):2819–32.PubMedPubMedCentralCrossRef
46.
Zhang J, Zhao X, Zhang J, Zheng X, Li F. Circular RNA hsa_circ_0023404 exerts an oncogenic role in cervical cancer through regulating miR-136/TFCP2/YAP pathway. Biochem Biophys Res Commun. 2018;501(2):428–33.PubMedCrossRef
47.
Hong H, Zhu H, Zhao S, Wang K, Zhang N, Tian Y, Li Y, Wang Y, Lv X, Wei T, et al. The novel circCLK3/miR-320a/FoxM1 axis promotes cervical cancer progression. Cell Death Dis. 2019;10(12):950.PubMedPubMedCentralCrossRef
48.
Tang Q, Chen Z, Zhao L. Correction for: circular RNA hsa_circ_0000515 acts as a miR-326 sponge to promote cervical cancer progression through up-regulation of ELK1. Aging. 2020;12(4):4040.PubMedPubMedCentralCrossRef
49.
50.
Wang J, Li H, Liang Z. circ-MYBL2 serves as a sponge for miR-361-3p promoting cervical cancer cells proliferation and invasion. Onco Targets Ther. 2019;12:9957–64.PubMedPubMedCentralCrossRef
51.
Li W, Jiang W, Liu T, Lv J, Guan J. Enhanced expression of circ_0000735 forecasts clinical severity in NSCLC and promotes cell progression via sponging miR-1179 and miR-1182. Biochem Biophys Res Commun. 2019;510(3):467–71.PubMedCrossRef
52.
Yang Y, Ding L, Li Y, Xuan C. Hsa_circ_0039411 promotes tumorigenesis and progression of papillary thyroid cancer by miR-1179/ABCA9 and miR-1205/MTA1 signaling pathways. J Cell Physiol. 2020;235(2):1321–9.PubMedCrossRef
53.
An J, Shi H, Zhang N, Song S. Elevation of circular RNA circ_0003645 forecasts unfavorable prognosis and facilitates cell progression via miR-1179/TMEM14A pathway in non-small cell lung cancer. Biochem Biophys Res Commun. 2019;511(4):921–5.PubMedCrossRef
54.
Ye M, Hou H, Shen M, Dong S, Zhang T. Circular RNA circFOXM1 plays a role in papillary thyroid carcinoma by sponging miR-1179 and regulating HMGB1 expression. Mol Ther Nucleic Acids. 2020;19:741–50.PubMedCrossRef
55.
Tang Z, Li L, Tang Y, Xie D, Wu K, Wei W, Xiao Q. CDK2 positively regulates aerobic glycolysis by suppressing SIRT5 in gastric cancer. Cancer Sci. 2018;109(8):2590–8.PubMedPubMedCentralCrossRef
56.
Chen Y, Du J, Wang Y, Shi H, Jiang Q, Wang Y, Zhang H, Wei Y, Xue W, Pu Z, et al. MicroRNA-497-5p induces cell cycle arrest of cervical cancer cells in S phase by targeting CBX4. Onco Targets Ther. 2019;12:10535–45.PubMedPubMedCentralCrossRef
57.
Mok MT, Zhou J, Tang W, Zeng X, Oliver AW, Ward SE, Cheng AS. CCRK is a novel signalling hub exploitable in cancer immunotherapy. Pharmacol Ther. 2018;186:138–51.PubMedCrossRef
58.
Tadesse S, Caldon EC, Tilley W, Wang S. Cyclin-dependent kinase 2 inhibitors in cancer therapy: an update. J Med Chem. 2019;62(9):4233–51.PubMedCrossRef
59.
Zhang Q, Miao S, Han X, Li C, Zhang M, Cui K, Xiong T, Chen Z, Wang C, Xu H. MicroRNA-3619-5p suppresses bladder carcinoma progression by directly targeting beta-catenin and CDK2 and activating p21. Cell Death Dis. 2018;9(10):960.PubMedPubMedCentralCrossRef
60.
Xie B, Zhao Z, Liu Q, Wang X, Ma Z, Li H. CircRNA has_circ_0078710 acts as the sponge of microRNA-31 involved in hepatocellular carcinoma progression. Gene. 2019;683:253–61.PubMedCrossRef
61.
Du WW, Yang W, Liu E, Yang Z, Dhaliwal P, Yang BB. Foxo3 circular RNA retards cell cycle progression via forming ternary complexes with p21 and CDK2. Nucleic Acids Res. 2016;44(6):2846–58.PubMedPubMedCentralCrossRef
Metadata
Title
circ_0084927 promotes cervical carcinogenesis by sponging miR-1179 that suppresses CDK2, a cell cycle-related gene
Authors
Xinhua Qu
Liumei Zhu
Linlin Song
Shaohua Liu
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2020
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-020-01417-2

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