Skip to main content
SpringerLink
Log in

A Functional Polymorphism in the Promoter of miR-17-92 is Associated with a Reduced Risk of Cervical Squamous Cell Carcinoma

  • Original Article
  • Published:
Reproductive Sciences Aims and scope Submit manuscript

Abstract

miR-17-92 cluster was differentially expressed in cervical cancer, playing an important role in regulating cell proliferation, apoptosis, migration, and invasion. The purpose of this study was to investigate the association between polymorphisms (i.e., rs9588884, rs982873, and rs1813389) in the promoter of miR-17-92 and the risk of cervical squamous cell carcinoma (CSCC). The rs9588884 polymorphism was genotyped using a Taqman assay and the rs982873 and rs1813389 polymorphisms were genotyped using a polymerase chain reaction-restriction fragment length polymorphism method. The expression levels of miR-17-92 were determined using a quantitative PCR analysis. The rs9588884 GG genotype was associated with a reduced risk of CSCC in homozygote comparison (adjusted OR = 0.47, 95% CI, 0.30–0.75, P = 0.001), dominant model (adjusted OR = 0.67, 95% CI, 0.50–0.91, P = 0.01), and recessive model (adjusted OR = 0.57, 95% CI, 0.38–0.85, P = 0.01). The rs9588884 G allele was also associated with a reduced risk of CSCC in allele comparison (adjusted OR = 0.71, 95% CI, 0.58–0.88, P = 0.002). Moreover, patients with the rs9588884 GG genotype had lower levels of miR-20a compared with the rs9588884 CC genotype (P = 0.03). These findings indicate that the rs9588884 GG genotype was associated with lower levels of miR-20a and eventually related to the risk of CSCC in Chinese women.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394–424.

    Article  Google Scholar 

  2. Otter S, Whitaker S, Chatterjee J, Stewart A. The human papillomavirus as a common pathogen in oropharyngeal, anal and cervical cancers. Clin Oncol (R Coll Radiol). 2019;31:81–90.

    Article  CAS  Google Scholar 

  3. Berman TA, Schiller JT. Human papillomavirus in cervical cancer and oropharyngeal cancer: one cause, two diseases. Cancer. 2017;123:2219–29.

    Article  Google Scholar 

  4. Wardak S. Human Papillomavirus (HPV) and cervical cancer. Med Dosw Mikrobiol. 2016;68:73–84.

    PubMed  Google Scholar 

  5. Gadducci A, Barsotti C, Cosio S, Domenici L, Riccardo GA. Smoking habit, immune suppression, oral contraceptive use, and hormone replacement therapy use and cervical carcinogenesis: a review of the literature. Gynecol Endocrinol. 2011;27:597–604.

    Article  Google Scholar 

  6. Ruan K, Fang X, Ouyang G. MicroRNAs: novel regulators in the hallmarks of human cancer. Cancer Lett. 2009;285:116–26.

    Article  CAS  Google Scholar 

  7. Kang HW, Wang F, Wei Q, Zhao YF, Liu M, Li X, et al. miR-20a promotes migration and invasion by regulating TNKS2 in human cervical cancer cells. FEBS Lett. 2012;586:897–904.

    Article  CAS  Google Scholar 

  8. Servin-Gonzalez LS, Granados-Lopez AJ, Lopez JA. Families of microRNAs expressed in clusters regulate cell signaling in cervical cancer. Int J Mol Sci. 2015;16:12773–90.

    Article  Google Scholar 

  9. Konicke K, Lopez-Luna A, Munoz-Carrillo JL, et al. The microRNA landscape of cutaneous squamous cell carcinoma. Drug Discov Today. 2018;23:864–70.

    Article  CAS  Google Scholar 

  10. Cheung TH, Man KN, Yu MY, Yim SF, Siu NS, Lo KW, et al. Dysregulated microRNAs in the pathogenesis and progression of cervical neoplasm. Cell Cycle. 2012;11:2876–84.

    Article  CAS  Google Scholar 

  11. Wei Q, Li YX, Liu M, Li X, Tang H. MiR-17-5p targets TP53INP1 and regulates cell proliferation and apoptosis of cervical cancer cells. IUBMB Life. 2012;64:697–704.

    Article  CAS  Google Scholar 

  12. Xu XM, Wang XB, Chen MM, Liu T, Li YX, Jia WH, et al. MicroRNA-19a and -19b regulate cervical carcinoma cell proliferation and invasion by targeting CUL5. Cancer Lett. 2012;322:148–58.

    Article  CAS  Google Scholar 

  13. Rao Q, Shen Q, Zhou H, Peng Y, Li J, Lin Z. Aberrant microRNA expression in human cervical carcinomas. Med Oncol. 2012;29:1242–8.

    Article  CAS  Google Scholar 

  14. Chen J, Yao D, Li Y, Chen H, He C, Ding N, et al. Serum microRNA expression levels can predict lymph node metastasis in patients with early-stage cervical squamous cell carcinoma. Int J Mol Med. 2013;32:557–67.

    Article  CAS  Google Scholar 

  15. Zhao S, Yao DS, Chen JY, Ding N. Aberrant expression of miR-20a and miR-203 in cervical cancer. Asian Pac J Cancer Prev. 2013;14:2289–93.

    Article  Google Scholar 

  16. Zhou Q, Dong J, Luo R, Zhou X, Wang J, Chen F. MicroRNA-20a regulates cell proliferation, apoptosis and autophagy by targeting thrombospondin 2 in cervical cancer. Eur J Pharmacol. 2019;844:102–9.

    Article  CAS  Google Scholar 

  17. Zhao S, Yao D, Chen J, Ding N, Ren F. MiR-20a promotes cervical cancer proliferation and metastasis in vitro and in vivo. PLoS One. 2015;10:e0120905.

    Article  Google Scholar 

  18. Liu J, Ni S. Association between genetic polymorphisms in the promoters of let-7 and risk of cervical squamous cell carcinoma. Gene. 2018;642:256–60.

    Article  CAS  Google Scholar 

  19. Wang S, Cao X, Ding B, Chen J, Cui M, Xu Y, et al. The rs767649 polymorphism in the promoter of miR-155 contributes to the decreased risk for cervical cancer in a Chinese population. Gene. 2016;595:109–14.

    Article  CAS  Google Scholar 

  20. Liang Y, Sun R, Li L, et al. A functional polymorphism in the promoter of MiR-143/145 is associated with the risk of cervical squamous cell carcinoma in Chinese women: a case-control study. Medicine (Baltimore). 2015;94:e1289.

    Article  CAS  Google Scholar 

  21. Huang J, Ni S, Li D, He Y. An insertion/deletion polymorphism at miRNA-122 binding site in the IL1A is associated with a reduced risk of cervical squamous cell carcinoma. Genet Test Mol Biomarkers. 2015;19:331–4.

    Article  CAS  Google Scholar 

  22. Sun R, Liang Y, Yuan F, Nie X, Sun H, Wang Y, et al. Functional polymorphisms in the promoter region of miR-17-92 cluster are associated with a decreased risk of colorectal cancer. Oncotarget. 2017;8:82531–40.

    PubMed  PubMed Central  Google Scholar 

  23. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001;25:402–8.

    Article  CAS  Google Scholar 

  24. Nair VB, Manasa VG, Sinto MS, Jayasree K, James FV, Kannan S. Differential expression of microRNAs in uterine cervical cancer and its implications in carcinogenesis: an integrative approach. Int J Gynecol Cancer. 2018;28:553–62.

    Article  Google Scholar 

  25. Pedroza-Torres A, Lopez-Urrutia E, Garcia-Castillo V, et al. MicroRNAs in cervical cancer: evidences for a miRNA profile deregulated by HPV and its impact on radio-resistance. Molecules. 2014;19:6263–81.

    Article  Google Scholar 

  26. Ding H, Wu YL, Wang YX, Zhu FF. Characterization of the microRNA expression profile of cervical squamous cell carcinoma metastases. Asian Pac J Cancer Prev. 2014;15:1675–9.

    Article  Google Scholar 

  27. Sand M, Hessam S, Amur S, Skrygan M, Bromba M, Stockfleth E, et al. Expression of oncogenic miR-17-92 and tumor suppressive miR-143-145 clusters in basal cell carcinoma and cutaneous squamous cell carcinoma. J Dermatol Sci. 2017;86:142–8.

    Article  CAS  Google Scholar 

  28. Chhabra R. let-7i-5p, miR-181a-2-3p and EGF/PI3K/SOX2 axis coordinate to maintain cancer stem cell population in cervical cancer. Sci Rep. 2018;8:7840.

    Article  Google Scholar 

  29. Chen Y, Ma C, Zhang W, Chen Z, Ma L. Down regulation of miR-143 is related with tumor size, lymph node metastasis and HPV16 infection in cervical squamous cancer. Diagn Pathol. 2014;9:88.

    Article  Google Scholar 

  30. Liu L, Yu X, Guo X, et al. miR-143 is downregulated in cervical cancer and promotes apoptosis and inhibits tumor formation by targeting Bcl-2. Mol Med Rep. 2012;5:753–60.

    Article  CAS  Google Scholar 

  31. Chen Z, Han Y, Song C, Wei H, Chen Y, Huang K, et al. Systematic review and meta-analysis of the prognostic significance of microRNAs in cervical cancer. Oncotarget. 2018;9:17141–8.

    PubMed  Google Scholar 

  32. Wei H, Wen-Ming C, Jun-Bo J. Plasma miR-145 as a novel biomarker for the diagnosis and radiosensitivity prediction of human cervical cancer. J Int Med Res. 2017;45:1054–60.

    Article  Google Scholar 

  33. Lu H, He Y, Lin L, Qi Z, Ma L, Li L, et al. Long non-coding RNA MALAT1 modulates radiosensitivity of HR-HPV+ cervical cancer via sponging miR-145. Tumour Biol. 2016;37:1683–91.

    Article  CAS  Google Scholar 

  34. Fang H, Shuang D, Yi Z, Sheng H, Liu Y. Up-regulated microRNA-155 expression is associated with poor prognosis in cervical cancer patients. Biomed Pharmacother. 2016;83:64–9.

    Article  CAS  Google Scholar 

  35. Wang F, Shan S, Huo Y, Xie Z, Fang Y, Qi Z, et al. MiR-155-5p inhibits PDK1 and promotes autophagy via the mTOR pathway in cervical cancer. Int J Biochem Cell Biol. 2018;99:91–9.

    Article  CAS  Google Scholar 

Download references

Author information

Author notes

  1. Juan Huang and Shanshan Ni contributed equally to this work.

Authors and Affiliations

  1. Department of Obstetrics and Gynaecology, Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China , Chengdu, 611731, Sichuan, People’s Republic of China

    Juan Huang & Rong Tang

  2. Department of Gynecology, Tianjin Central Hospital of Gynecology and Obstetrics, Tianjin, 300100, People’s Republic of China

    Shanshan Ni

Authors
  1. Juan Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shanshan Ni
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Rong Tang
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

HJ designed and wrote the manuscript. Ni S performed sample collection and performed experiments. Tang R performed statistical analysis.

Corresponding author

Correspondence to Juan Huang.

Ethics declarations

This study was carried out in accordance with the recommendations of the Institutional Human Ethics Committee of the Chengdu Women’s and Children’s Central Hospital with written informed consent from all subjects. All subjects gave written informed consent in accordance with the Declaration of Helsinki. The protocol was approved by the Institutional Human Ethics Committee of the Chengdu Women’s and Children’s Central Hospital.

Conflict of Interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Huang, J., Ni, S. & Tang, R. A Functional Polymorphism in the Promoter of miR-17-92 is Associated with a Reduced Risk of Cervical Squamous Cell Carcinoma. Reprod. Sci. 27, 87–92 (2020). https://doi.org/10.1007/s43032-019-00007-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s43032-019-00007-6

Keywords

Search

Navigation