A Functional Variant Rs2072915 is Associated with the Susceptibility and Mortality of Cervical Squamous Cell Carcinoma

Overview

Journal Pharmgenomics Pers Med

Publisher Dove Medical Press

Date 2021 Jun 24

PMID 34163215

Authors

Ren-Liang Li

Jiao-Hong Wu

Min Guo

Li-Xiao Sha

Shu-Qi Xia

Lian Xu

Affiliations

Soon will be listed here.

Abstract

Purpose: Genetic variant has been demonstrated to be a risk factor for the occurrence and outcome of cervical squamous cell carcinoma (CSCC). From previous genome wide association studies, 6p21.32 has been identified as a susceptibility locus of CSCC. The purpose of this study was to investigate the association of a polymorphism rs2072915 located in 6p21.32 with the risk of CSCC and examine the potential mechanism of the rs2072915 in CSCC pathogenesis.

Patients And Methods: The rs2072915 was genotyped using polymerase chain reaction (PCR)-restriction fragment length polymorphism. miR-637 and mRNA expression levels in CSCC patients were examined using quantitative PCR. miR-637 target site was determined using the dual-luciferase reporter assay.

Results: The rs2072915 was associated with a significantly increased risk (AA vs TT: adjusted OR = 2.48, 95% CI, 1.57-3.94, < 0.001; AT/AA vs TT: adjusted OR = 1.38, 95% CI, 1.06-1.80, = 0.018; A vs T: adjusted OR = 1.49, 95% CI, 1.21-1.84, < 0.001, respectively) and shorter survival time of CSCC ( = 0.03). Patients with the rs2072915 AA genotype displayed lower levels of that is a target of miR-637.

Conclusion: These findings suggest that the rs2072915 T > A change might augment the binding energy of miR-637 to , result in lower levels of , and thus contribute to the risk of CSCC.

References

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(6):331-4. DOI: 10.1089/gtmb.2015.0015. View

Bosch F, Lorincz A, Munoz N, Meijer C, Shah K . The causal relation between human papillomavirus and cervical cancer. J Clin Pathol. 2002; 55(4):244-65. PMC: 1769629. DOI: 10.1136/jcp.55.4.244. View

Lee S, Lee J, Choi J, Lee S, Park J, Kim D . Epigenetic inactivation of retinoid X receptor genes in non-small cell lung cancer and the relationship with clinicopathologic features. Cancer Genet Cytogenet. 2010; 197(1):39-45. DOI: 10.1016/j.cancergencyto.2009.10.008. View

Chen W, Zheng R, Baade P, Zhang S, Zeng H, Bray F . Cancer statistics in China, 2015. CA Cancer J Clin. 2016; 66(2):115-32. DOI: 10.3322/caac.21338. View

Wang F, Liu M, Li X, Tang H . MiR-214 reduces cell survival and enhances cisplatin-induced cytotoxicity via down-regulation of Bcl2l2 in cervical cancer cells. FEBS Lett. 2013; 587(5):488-95. DOI: 10.1016/j.febslet.2013.01.016. View

Hang D, Zhou W, Jia M, Wang L, Zhou J, Yin Y . Genetic variants within microRNA-binding site of RAD51B are associated with risk of cervical cancer in Chinese women. Cancer Med. 2016; 5(9):2596-601. PMC: 5055154. DOI: 10.1002/cam4.797. View

Livak K, Schmittgen T . Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2002; 25(4):402-8. DOI: 10.1006/meth.2001.1262. View

Zheng Y, Nie P, Peng D, He Z, Liu M, Xie Y . m6AVar: a database of functional variants involved in m6A modification. Nucleic Acids Res. 2017; 46(D1):D139-D145. PMC: 5753261. DOI: 10.1093/nar/gkx895. View

Walboomers J, Jacobs M, Manos M, Bosch F, Kummer J, Shah K . Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol. 1999; 189(1):12-9. DOI: 10.1002/(SICI)1096-9896(199909)189:1<12::AID-PATH431>3.0.CO;2-F. View

10.

Schiffman M, Wentzensen N, Wacholder S, Kinney W, Gage J, Castle P . Human papillomavirus testing in the prevention of cervical cancer. J Natl Cancer Inst. 2011; 103(5):368-83. PMC: 3046952. DOI: 10.1093/jnci/djq562. View

11.

Guo X, Dong Z, Yamada S, Li Y, Guo Y, Shen S . Association of Casp3 microRNA Target Site (1049216) SNP With the Risk and Progress of Cervical Squamous Cell Carcinoma. Int J Gynecol Cancer. 2017; 27(2):206-213. DOI: 10.1097/IGC.0000000000000881. View

12.

Miura K, Mishima H, Yasunami M, Kaneuchi M, Kitajima M, Abe S . A significant association between rs8067378 at 17q12 and invasive cervical cancer originally identified by a genome-wide association study in Han Chinese is replicated in a Japanese population. J Hum Genet. 2016; 61(9):793-6. DOI: 10.1038/jhg.2016.50. View

13.

Li J, Xiao X, Zhang Y, Wang Y, Feng L, Wu Y . MicroRNA miR-886-5p inhibits apoptosis by down-regulating Bax expression in human cervical carcinoma cells. Gynecol Oncol. 2010; 120(1):145-51. DOI: 10.1016/j.ygyno.2010.09.009. View

14.

Zhou X, Shan L, Na J, Li Y, Wang J . The SNP rs4846048 of MTHFR enhances the cervical cancer risk through association with miR-522: A preliminary report. Mol Genet Genomic Med. 2019; 8(1):e1055. PMC: 6978235. DOI: 10.1002/mgg3.1055. View

15.

Shi Y, Li L, Hu Z, Li S, Wang S, Liu J . A genome-wide association study identifies two new cervical cancer susceptibility loci at 4q12 and 17q12. Nat Genet. 2013; 45(8):918-22. DOI: 10.1038/ng.2687. View

16.

Munoz N, Bosch F, de Sanjose S, Herrero R, Castellsague X, Shah K . Epidemiologic classification of human papillomavirus types associated with cervical cancer. N Engl J Med. 2003; 348(6):518-27. DOI: 10.1056/NEJMoa021641. View

17.

Ke G, Liang L, Yang J, Huang X, Han D, Huang S . MiR-181a confers resistance of cervical cancer to radiation therapy through targeting the pro-apoptotic PRKCD gene. Oncogene. 2012; 32(25):3019-27. DOI: 10.1038/onc.2012.323. View

18.

Sticht C, de la Torre C, Parveen A, Gretz N . miRWalk: An online resource for prediction of microRNA binding sites. PLoS One. 2018; 13(10):e0206239. PMC: 6193719. DOI: 10.1371/journal.pone.0206239. View

19.

Yu A, Zhang J, Mei Y, Zhong H, Chen S, Song Q . Correlation Between Single Nucleotide Polymorphisms of an miRNA Binding Site in the 3'UTR of and Risk of Cervical Cancer Among the Han Chinese. Genet Test Mol Biomarkers. 2020; 24(7):381-389. DOI: 10.1089/gtmb.2019.0269. View

20.

Mathonnet G, Fabian M, Svitkin Y, Parsyan A, Huck L, Murata T . MicroRNA inhibition of translation initiation in vitro by targeting the cap-binding complex eIF4F. Science. 2007; 317(5845):1764-7. DOI: 10.1126/science.1146067. View