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Current Molecular Pharmacology

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ISSN (Print): 1874-4672
ISSN (Online): 1874-4702

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Research Article

Hsa_Circ_0000021 Sponges miR-3940-3p/KPNA2 Expression to Promote Cervical Cancer Progression

Author(s): Qingyuan Zeng, Kun Feng, Yang Yu and Yumei Lv*

Volume 17, 2024

Published on: 03 May, 2023

Article ID: e170223213775 Pages: 13

DOI: 10.2174/1874467216666230217151946

Price: $65

Abstract

Background: Circular RNAs (circRNAs) have a vital role in the occurrence of numerous cancers. However, its function and pattern of expression in cervical cancer (CC) remain unclear. This research aims to investigate the hsa_circ_000002’s regulatory mechanism in CC.

Methods: Hsa_circ_0000021, miR-3940-3p, and KPNA2 expression levels were estimated through qRT-PCR. Nuclear/cytoplasmic separation was conducted to find the subcellular location of hsa_circ_0000021. Western blot was done to estimate the levels of KPNA2 protein. CCK-8, BrdU, wound healing, transwell, and tumor xenograft assays were performed to study how hsa_circ_0000021/miR-3940-3P/KPNA2 function affect CC. Hsa_circ_0000021’s targeting relationships with miR-3940-3p and KPNA2 were ascertained through RIP and luciferase experiments.

Results: Hsa_circ_0000021 and KPNA2 were overexpressed and inversely associated with the levels of miR-3940-3p in CC. Knocking down either hsa_circ_0000021 or KPNA2 repressed the growth of CC tumors as well as the proliferation, invasion, and migration of CC cells. Silencing miR-3940-3p promoted the malignant proliferation of CC cells. Regarding its mechanism, hsa_circ_0000021 affected the malignant CC cell proliferation via the sponging of miR-3940-3p, which targeted KPNA2.

Conclusion: Hsa_circ_0000021 regulates the miR-3940-3p/KPNA2 axis to promote CC occurrence. This potentially is a novel target for CC treatment.

[1]
Bray, F.; Ferlay, J.; Soerjomataram, I.; Siegel, R.L.; Torre, L.A.; Jemal, A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin., 2018, 68(6), 394-424.
[http://dx.doi.org/10.3322/caac.21492] [PMID: 30207593]
[2]
Berkowitz, R.P. 2012 updated consensus guidelines for the management of abnormal cervical cancer screening tests and cancer precursors. Obstet. Gynecol., 2013, 122(2), 393.
[http://dx.doi.org/10.1097/AOG.0b013e31829b61d6] [PMID: 23969811]
[3]
Chelimo, C.; Wouldes, T.A.; Cameron, L.D.; Elwood, J.M. Risk factors for and prevention of human papillomaviruses (HPV), genital warts and cervical cancer. J. Infect., 2013, 66(3), 207-217.
[http://dx.doi.org/10.1016/j.jinf.2012.10.024] [PMID: 23103285]
[4]
Bhatla, N.; Singhal, S. Primary HPV screening for cervical cancer. Best Pract. Res. Clin. Obstet. Gynaecol., 2020, 65, 98-108.
[http://dx.doi.org/10.1016/j.bpobgyn.2020.02.008] [PMID: 32291178]
[5]
Scarth, J.A.; Patterson, M.R.; Morgan, E.L.; Macdonald, A. The human papillomavirus oncoproteins: a review of the host pathways targeted on the road to transformation. J. Gen. Virol., 2021, 102(3), 001540.
[http://dx.doi.org/10.1099/jgv.0.001540] [PMID: 33427604]
[6]
Machalek, D.A; Wark, J.D; Tabrizi, S.N; Hopper, J.L; Bui, M.; Dite, G.S Genetic and environmental factors in invasive cervical cancer: Design and methods of a classical twin study. Twin Res. Hum. Genet., 2017, 20(1), 10-18.
[7]
Serviss, J.T.; Johnsson, P.; Grandér, D. An emerging role for long non-coding RNAs in cancer metastasis. Front. Genet., 2014, 5, 234.
[http://dx.doi.org/10.3389/fgene.2014.00234] [PMID: 25101115]
[8]
Aalijahan, H.; Ghorbian, S. Long non-coding RNAs and cervical cancer. Exp. Mol. Pathol., 2019, 106, 7-16.
[http://dx.doi.org/10.1016/j.yexmp.2018.11.010] [PMID: 30471246]
[9]
Cheng, H.; Tian, J.; Wang, C.; Ren, L.; Wang, N. LncRNA BLACAT1 is upregulated in Cervical Squamous Cell Carcinoma (CSCC) and predicts poor survival. Reprod. Sci., 2020, 27(2), 585-591.
[http://dx.doi.org/10.1007/s43032-019-00058-9] [PMID: 32046460]
[10]
Liu, Q.; Liu, S.; Wang, X.; Zhang, J.; Liu, K. LncRNA MAGI2-AS3 is involved in cervical squamous cell carcinoma development through CDK6 up-regulation. Infect. Agent. Cancer, 2019, 14(1), 37.
[http://dx.doi.org/10.1186/s13027-019-0238-5] [PMID: 31832086]
[11]
Zhou, R.S.; Zhang, E.X.; Sun, Q.F.; Ye, Z.J.; Liu, J.W.; Zhou, D.H.; Tang, Y. Integrated analysis of lncRNA-miRNA-mRNA ceRNA network in squamous cell carcinoma of tongue. BMC Cancer, 2019, 19(1), 779.
[http://dx.doi.org/10.1186/s12885-019-5983-8] [PMID: 31391008]
[12]
Yang, Y.; Yu, Q.; Li, B.; Guan, R.; Huang, C.; Yang, X. Retracted article: BBOX1-AS1 accelerates gastric cancer proliferation by sponging miR-3940-3p to upregulate BIRC5 expression. Dig. Dis. Sci., 2021, 66(4), 1054-1062.
[http://dx.doi.org/10.1007/s10620-020-06308-0] [PMID: 32394331]
[13]
Zan, Y.; Wang, B.; Liang, L.; Deng, Y.; Tian, T.; Dai, Z.; Dong, L. MicroRNA-139 inhibits hepatocellular carcinoma cell growth through down-regulating karyopherin alpha 2. J. Exp. Clin. Cancer Res., 2019, 38(1), 182.
[http://dx.doi.org/10.1186/s13046-019-1175-2] [PMID: 31046781]
[14]
Guo, X.; Wang, Z.; Zhang, J.; Xu, Q.; Hou, G.; Yang, Y.; Dong, C.; Liu, G.; Liang, C.; Liu, L.; Zhou, W.; Liu, H. Upregulated KPNA2 promotes hepatocellular carcinoma progression and indicates prognostic significance across human cancer types. Acta Biochim. Biophys. Sin., 2019, 51(3), 285-292.
[http://dx.doi.org/10.1093/abbs/gmz003] [PMID: 30883648]
[15]
Christiansen, A.; Dyrskjøt, L. The functional role of the novel biomarker karyopherin α 2 (KPNA2) in cancer. Cancer Lett., 2013, 331(1), 18-23.
[http://dx.doi.org/10.1016/j.canlet.2012.12.013] [PMID: 23268335]
[16]
Yang, Z.; Li, C.; Fan, X.Y.; Liu, L.J. Circular RNA circ_0079593 promotes glioma development through regulating KPNA2 expression by sponging miR-499a-5p. Eur. Rev. Med. Pharmacol. Sci., 2020, 24(3), 1288-1301.
[PMID: 32096160]
[17]
Chen, R.; Mao, L.; Shi, R.; Wang, W.; Cheng, J. circRNA MYLK accelerates cervical cancer via up-regulation of RHEB and activation of mTOR signaling. Cancer Manag. Res., 2020, 12, 3611-3621.
[http://dx.doi.org/10.2147/CMAR.S238172] [PMID: 32547198]
[18]
Cai, Y.; Li, C.; Peng, F.; Yin, S.; Liang, H.; Su, J.; Li, L.; Yang, A.; Liu, H.; Yang, C.; Luo, D.; Xia, C. D. ownregulation of hsa_circRNA_0001400 helps to promote cell apoptosis through disruption of the circRNA_0001400-miR-326 sponge in cervical cancer cells. Front. Genet., 2021, 12, 779195.
[http://dx.doi.org/10.3389/fgene.2021.779195] [PMID: 34976014]
[19]
Zhang, Y.; Zhao, L.; Yang, S.; Cen, Y.; Zhu, T.; Wang, L.; Xia, L.; Liu, Y.; Zou, J.; Xu, J.; Li, Y.; Cheng, X.; Lu, W.; Wang, X.; Xie, X. CircCDKN2B-AS1 interacts with IMP3 to stabilize hexokinase 2 mRNA and facilitate cervical squamous cell carcinoma aerobic glycolysis progression. J. Exp. Clin. Cancer Res., 2020, 39(1), 281.
[http://dx.doi.org/10.1186/s13046-020-01793-7] [PMID: 33308298]
[20]
Song, J.; Ye, A.; Jiang, E.; Yin, X.; Chen, Z.; Bai, G.; Zhou, Y.; Liu, J. Reconstruction and analysis of the aberrant lncRNA-miRNA-mRNA network based on competitive endogenous RNA in CESC. J. Cell. Biochem., 2018, 119(8), 6665-6673.
[http://dx.doi.org/10.1002/jcb.26850] [PMID: 29741786]
[21]
Jin, J.; Chen, X.; Chen, J.; Geng, X. Long noncoding RNA MACC1-AS1 is a potential sponge of microRNA-34a in cervical squamous cell carcinoma and upregulates cyclin-dependent kinase 6. Oncol. Lett., 2020, 19(3), 2339-2345.
[http://dx.doi.org/10.3892/ol.2020.11346] [PMID: 32194733]
[22]
Lyv, X.; Wu, F.; Zhang, H.; Lu, J.; Wang, L.; Ma, Y. Long noncoding RNA ZFPM2-AS1 knockdown restrains the development of retinoblastoma by modulating the MicroRNA-515/HOXA1/Wnt/β-catenin axis. Invest. Ophthalmol. Vis. Sci., 2020, 61(6), 41.
[http://dx.doi.org/10.1167/iovs.61.6.41] [PMID: 32561925]
[23]
Jiang, H.; He, Q.; Liu, T. BBOX1-AS1 accelerates nasopharyngeal carcinoma progression by sponging miR-3940-3p and enhancing KPNA2 upregulation. Cancer Manag. Res., 2021, 13, 9049-9062.
[http://dx.doi.org/10.2147/CMAR.S327211] [PMID: 34938119]
[24]
Liu, Z.; Yang, S.; Zhou, S.; Dong, S.; Du, J. Prognostic value of lncRNA DRAIC and miR-3940-3p in lung adenocarcinoma and their effect on lung adenocarcinoma cell progression. Cancer Manag. Res., 2021, 13, 8367-8376.
[http://dx.doi.org/10.2147/CMAR.S320616] [PMID: 34764698]
[25]
Ma, J.; Zhang, L.; Shang, A.; Song, H.; Huo, J.; Zhang, M.; Jiang, L. LINC02163 promotes colorectal cancer progression via miR-511-3p/AKT3 axis. Artif. Cells Nanomed. Biotechnol., 2020, 48(1), 961-968.
[http://dx.doi.org/10.1080/21691401.2020.1773486] [PMID: 32524841]
[26]
van der Watt, P.J.; Maske, C.P.; Hendricks, D.T.; Parker, M.I.; Denny, L.; Govender, D.; Birrer, M.J.; Leaner, V.D. The Karyopherin proteins, Crm1 and Karyopherin β1, are overexpressed in cervical cancer and are critical for cancer cell survival and proliferation. Int. J. Cancer, 2009, 124(8), 1829-1840.
[http://dx.doi.org/10.1002/ijc.24146] [PMID: 19117056]
[27]
Zhang, Q.; Jin, X.; Shi, W.; Chen, X.; Pang, W.; Yu, X.; Yang, L. A long non-coding RNA LINC00461-dependent mechanism underlying breast cancer invasion and migration via the miR-144-3p/KPNA2 axis. Cancer Cell Int., 2020, 20(1), 137.
[http://dx.doi.org/10.1186/s12935-020-01221-y] [PMID: 32355466]
[28]
Tsai, M.M.; Huang, H.W.; Wang, C.S.; Lee, K.F.; Tsai, C.Y.; Lu, P.H.; Chi, H.C.; Lin, Y.H.; Kuo, L.M.; Lin, K.H. MicroRNA-26b inhibits tumor metastasis by targeting the KPNA2/c-jun pathway in human gastric cancer. Oncotarget, 2016, 7(26), 39511-39526.
[http://dx.doi.org/10.18632/oncotarget.8629] [PMID: 27078844]
[29]
Yang, F.; Li, S.; Cheng, Y.; Li, J.; Han, X. Karyopherin α 2 promotes proliferation, migration and invasion through activating NF-κB/p65 signaling pathways in melanoma cells. Life Sci., 2020, 252, 117611.
[http://dx.doi.org/10.1016/j.lfs.2020.117611] [PMID: 32243925]
[30]
Huang, L.; Zhou, Y.; Cao, X.P.; Lin, J.X.; Zhang, L.; Huang, S.T.; Zheng, M. KPNA2 promotes migration and invasion in epithelial ovarian cancer cells by inducing epithelial-mesenchymal transition via Akt/GSK-3β/Snail activation. J. Cancer, 2018, 9(1), 157-165.
[http://dx.doi.org/10.7150/jca.20879] [PMID: 29290781]

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