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Open Access 01-12-2021 | Nephroblastoma | Research

METTL14 gene polymorphisms decrease Wilms tumor susceptibility in Chinese children

Authors: Zhenjian Zhuo, Rui-Xi Hua, Huizhu Zhang, Huiran Lin, Wen Fu, Jinhong Zhu, Jiwen Cheng, Jiao Zhang, Suhong Li, Haixia Zhou, Huimin Xia, Guochang Liu, Wei Jia, Jing He

Published in: BMC Cancer | Issue 1/2021

Abstract

Background

Wilms tumor is a highly heritable malignancy. Aberrant METTL14, a critical component of N6-methyladenosine (m⁶A) methyltransferase, is involved in carcinogenesis. The association between genetic variants in the METTL14 gene and Wilms tumor susceptibility remains to be fully elucidated. We aimed to assess whether variants within this gene are implicated in Wilms tumor susceptibility.

Methods

A total of 403 patients and 1198 controls were analyzed. METTL14 genotypes were assessed by TaqMan genotyping assay.

Result

Among the five SNPs analyzed, rs1064034 T > A and rs298982 G > A exhibited a significant association with decreased susceptibility to Wilms tumor. Moreover, the joint analysis revealed that the combination of five protective genotypes exerted significantly more protective effects against Wilms tumor than 0–4 protective genotypes with an OR of 0.69. The stratified analysis further identified the protective effect of rs1064034 T > A, rs298982 G > A, and combined five protective genotypes in specific subgroups. The above significant associations were further validated by haplotype analysis and false-positive report probability analysis. Preliminary mechanism exploration indicated that rs1064034 T > A and rs298982 G > A are correlated with the expression and splicing event of their surrounding genes.

Conclusions

Collectively, our results suggest that METTL14 gene SNPs may be genetic modifiers for the development of Wilms tumor.

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Aldrink JH, Heaton TE, Dasgupta R, Lautz TB, Malek MM, Abdessalam SF, et al. Update on Wilms tumor. J Pediatr Surg. 2019;54:390–7.PubMedCrossRef

Phelps HM, Kaviany S, Borinstein SC, Lovvorn HN 3rd. Biological Drivers of Wilms Tumor Prognosis and Treatment. Children (Basel). 2018;5:145.

Breslow N, Olshan A, Beckwith JB, Green DM. Epidemiology of Wilms tumor. Med Pediatr Oncol. 1993;21:172–81.PubMedCrossRef

Bao PP, Li K, Wu CX, Huang ZZ, Wang CF, Xiang YM, et al. Recent incidences and trends of childhood malignant solid tumors in Shanghai, 2002-2010. Zhonghua Er Ke Za Zhi. 2013;51:288–94.PubMed

Hohenstein P, Pritchard-Jones K, Charlton J. The yin and yang of kidney development and Wilms’ tumors. Genes Dev. 2015;29:467–82.PubMedPubMedCentralCrossRef

Dome JS, Graf N, Geller JI, Fernandez CV, Mullen EA, Spreafico F, et al. Advances in Wilms tumor treatment and biology: Progress through international collaboration. J Clin Oncol. 2015;33:2999–3007.PubMedPubMedCentralCrossRef

Spiegl HR, Murphy AJ, Yanishevski D, Brennan RC, Li C, Lu Z, et al. Complications following nephron-sparing surgery for Wilms tumor. J Pediatr Surg. 2020;55:126–9.PubMedCrossRef

Saltzman AF, Carrasco A Jr, Amini A, Cost NG. Patterns of care and survival comparison of adult and pediatric Wilms tumor in the United States: a study of the National Cancer Database. Urology. 2020;135:50–6.PubMedCrossRef

Sonn G, Shortliffe LM. Management of Wilms tumor: current standard of care. Nat Clin Pract Urol. 2008;5:551–60.PubMedCrossRef

10.

Wong KF, Reulen RC, Winter DL, Guha J, Fidler MM, Kelly J, et al. Risk of adverse health and social outcomes up to 50 years after Wilms tumor: the British childhood Cancer survivor study. J Clin Oncol. 2016;34:1772–9.PubMedCrossRef

11.

Haber DA, Buckler AJ, Glaser T, Call KM, Pelletier J, Sohn RL, et al. An internal deletion within an 11p13 zinc finger gene contributes to the development of Wilms’ tumor. Cell. 1990;61:1257–69.PubMedCrossRef

12.

Pelletier J, Bruening W, Li FP, Haber DA, Glaser T, Housman DE. WT1 mutations contribute to abnormal genital system development and hereditary Wilms’ tumour. Nature. 1991;353:431–4.PubMedCrossRef

13.

Treger TD, Chowdhury T, Pritchard-Jones K, Behjati S. The genetic changes of Wilms tumour. Nat Rev Nephrol. 2019;15:240–51.PubMedCrossRef

14.

Ruteshouser EC, Robinson SM, Huff V. Wilms tumor genetics: mutations in WT1, WTX, and CTNNB1 account for only about one-third of tumors. Genes Chromosomes Cancer. 2008;47:461–70.PubMedPubMedCentralCrossRef

15.

Turnbull C, Perdeaux ER, Pernet D, Naranjo A, Renwick A, Seal S, et al. A genome-wide association study identifies susceptibility loci for Wilms tumor. Nat Genet. 2012;44:681–4.PubMedPubMedCentralCrossRef

16.

Fu W, Zhuo Z, Hua RX, Fu K, Jia W, Zhu J, et al. Association of KRAS and NRAS gene polymorphisms with Wilms tumor risk: a four-center case-control study. Aging (Albany NY). 2019;11:1551–63.CrossRef

17.

Liu GC, Zhuo ZJ, Zhu SB, Zhu J, Jia W, Zhao Z, et al. Associations between LMO1 gene polymorphisms and Wilms’ tumor susceptibility. Oncotarget. 2017;8:50665–72.PubMedPubMedCentralCrossRef

18.

Liu P, Zhuo Z, Li W, Cheng J, Zhou H, He J, et al. TP53 rs1042522 C>G polymorphism and Wilms tumor susceptibility in Chinese children: a four-center case-control study. Biosci Rep. 2019;39:BSR20181891.PubMedPubMedCentralCrossRef

19.

Ferrara M, Capozzi L, Russo R. Impact of the MTHFR C677T polymorphism on risk of Wilms tumor: case-control study. J Pediatr Hematol Oncol. 2009;31:256–8.PubMedCrossRef

20.

Cao G, Li HB, Yin Z, Flavell RA. Recent advances in dynamic m6A RNA modification. Open Biol. 2016;6:160003.PubMedPubMedCentralCrossRef

21.

Liang Y, Zhan G, Chang KJ, Yang YP, Wang L, Lin J, et al. The roles of m6A RNA modifiers in human cancer. J Chin Med Assoc. 2020;83:221–6.PubMedCrossRef

22.

Meyer KD, Jaffrey SR. Rethinking m (6) a readers, writers, and erasers. Annu Rev Cell Dev Biol. 2017;33:319–42.PubMedPubMedCentralCrossRef

23.

Tao L, Mu X, Chen H, Jin D, Zhang R, Zhao Y, et al. FTO modifies the m6A level of MALAT and promotes bladder cancer progression. Clin Transl Med. 2021;11:e310.PubMedPubMedCentralCrossRef

24.

Zhou C, Zhang Z, Zhu X, Qian G, Zhou Y, Sun Y, et al. N6-Methyladenosine modification of the TRIM7 positively regulates tumorigenesis and chemoresistance in osteosarcoma through ubiquitination of BRMS1. EBioMedicine. 2020;59:102955.PubMedPubMedCentralCrossRef

25.

Huang J, Chen Z, Chen X, Chen J, Cheng Z, Wang Z. The role of RNA N (6)-methyladenosine methyltransferase in cancers. Mol Ther Nucleic Acids. 2021;23:887–96.PubMedPubMedCentralCrossRef

26.

Ma L, Hua RX, Lin H, Zhu J, Fu W, Lin A, et al. The contribution of WTAP gene variants to Wilms tumor susceptibility. Gene. 2020;754:144839.PubMedCrossRef

27.

Hua RX, Liu J, Fu W, Zhu J, Zhang J, Cheng J, et al. ALKBH5 gene polymorphisms and Wilms tumor risk in Chinese children: a five-center case-control study. J Clin Lab Anal. 2020;34:e23251.PubMedPubMedCentralCrossRef

28.

Zhuo Z, Lu H, Zhu J, Hua RX, Li Y, Yang Z, et al. METTL14 gene polymorphisms confer neuroblastoma susceptibility: an eight-center case-control study. Mol Ther Nucleic Acids. 2020;22:17–26.PubMedPubMedCentralCrossRef

29.

Zhuo ZJ, Liu W, Zhang J, Zhu J, Zhang R, Tang J, et al. Functional polymorphisms at ERCC1/XPF genes confer neuroblastoma risk in Chinese children. EBioMedicine. 2018;30:113–9.PubMedPubMedCentralCrossRef

30.

Zhuo Z, Zhou C, Fang Y, Zhu J, Lu H, Zhou H, et al. Correlation between the genetic variants of base excision repair (BER) pathway genes and neuroblastoma susceptibility in eastern Chinese children. Cancer Commun (Lond). 2020;40:641–6.CrossRef

31.

Lin DY, Zeng D, Millikan R. Maximum likelihood estimation of haplotype effects and haplotype-environment interactions in association studies. Genet Epidemiol. 2005;29:299–312.PubMedCrossRef

32.

Hua RX, Zhuo Z, Ge L, Zhu J, Yuan L, Chen C, et al. LIN28A gene polymorphisms modify neuroblastoma susceptibility: a four-Centre case-control study. J Cell Mol Med. 2020;24:1059–66.PubMedCrossRef

33.

He J, Wang MY, Qiu LX, Zhu ML, Shi TY, Zhou XY, et al. Genetic variations of mTORC1 genes and risk of gastric cancer in an eastern Chinese population. Mol Carcinog. 2013;52(Suppl 1):E70–9.PubMedCrossRef

34.

Wacholder S, Chanock S, Garcia-Closas M, El Ghormli L, Rothman N. Assessing the probability that a positive report is false: an approach for molecular epidemiology studies. J Natl Cancer Inst. 2004;96:434–42.PubMedPubMedCentralCrossRef

35.

Carithers LJ, Moore HM. The genotype-tissue expression (GTEx) project. Biopreserv Biobank. 2015;13:307–8.PubMedPubMedCentralCrossRef

36.

Chen X, Xu M, Xu X, Zeng K, Liu X, Sun L, et al. METTL14 suppresses CRC progression via regulating N6-Methyladenosine-dependent primary miR-375 processing. Mol Ther. 2019;28:599–612.PubMedPubMedCentralCrossRef

37.

Ma JZ, Yang F, Zhou CC, Liu F, Yuan JH, Wang F, et al. METTL14 suppresses the metastatic potential of hepatocellular carcinoma by modulating N (6) -methyladenosine-dependent primary MicroRNA processing. Hepatology. 2017;65:529–43.PubMedCrossRef

38.

Weng H, Huang H, Wu H, Qin X, Zhao BS, Dong L, et al. METTL14 inhibits hematopoietic stem/progenitor differentiation and promotes Leukemogenesis via mRNA m (6) a modification. Cell Stem Cell. 2018;22:191–205 e9.PubMedCrossRef

39.

Lang F, Singh RK, Pei Y, Zhang S, Sun K, Robertson ES. EBV epitranscriptome reprogramming by METTL14 is critical for viral-associated tumorigenesis. PLoS Pathog. 2019;15:e1007796.PubMedPubMedCentralCrossRef

40.

Wang M, Liu J, Zhao Y, He R, Xu X, Guo X, et al. Upregulation of METTL14 mediates the elevation of PERP mRNA N (6) adenosine methylation promoting the growth and metastasis of pancreatic cancer. Mol Cancer. 2020;19:130.PubMedPubMedCentralCrossRef

41.

Meng Y, Li S, Gu D, Xu K, Du M, Zhu L, et al. Genetic variants in m6A modification genes are associated with colorectal cancer risk. Carcinogenesis. 2019;41:8–17.

42.

Akey J, Jin L, Xiong M. Haplotypes vs single marker linkage disequilibrium tests: what do we gain? Eur J Hum Genet. 2001;9:291–300.PubMedCrossRef

43.

Manolio TA, Brooks LD, Collins FS. A HapMap harvest of insights into the genetics of common disease. J Clin Invest. 2008;118:1590–605.PubMedPubMedCentralCrossRef

44.

Dong J, Teng F, Guo W, Yang J, Ding G, Fu Z. lncRNA SNHG8 promotes the tumorigenesis and metastasis by sponging miR-149-5p and predicts tumor recurrence in hepatocellular carcinoma. Cell Physiol Biochem. 2018;51:2262–74.PubMedCrossRef

45.

Qu X, Li Y, Wang L, Yuan N, Ma M, Chen Y. LncRNA SNHG8 accelerates proliferation and inhibits apoptosis in HPV-induced cervical cancer through recruiting EZH2 to epigenetically silence RECK expression. J Cell Biochem. 2020;121:4120–9.PubMedCrossRef

46.

Song H, Song J, Lu L, Li S. SNHG8 is upregulated in esophageal squamous cell carcinoma and directly sponges microRNA-411 to increase oncogenicity by upregulating KPNA2. Onco Targets Ther. 2019;12:6991–7004.PubMedPubMedCentralCrossRef

47.

Song Y, Zou L, Li J, Shen ZP, Cai YL, Wu XD. LncRNA SNHG8 promotes the development and chemo-resistance of pancreatic adenocarcinoma. Eur Rev Med Pharmacol Sci. 2018;22:8161–8.PubMed

48.

Zhen Y, Ye Y, Wang H, Xia Z, Wang B, Yi W, et al. Knockdown of SNHG8 repressed the growth, migration, and invasion of colorectal cancer cells by directly sponging with miR-663. Biomed Pharmacother. 2019;116:109000.PubMedCrossRef

Title: METTL14 gene polymorphisms decrease Wilms tumor susceptibility in Chinese children
Authors: Zhenjian Zhuo
Rui-Xi Hua
Huizhu Zhang
Huiran Lin
Wen Fu
Jinhong Zhu
Jiwen Cheng
Jiao Zhang
Suhong Li
Haixia Zhou
Huimin Xia
Guochang Liu
Wei Jia
Jing He
Publication date: 01-12-2021
Publisher: BioMed Central
Keyword: Nephroblastoma
Published in: BMC Cancer / Issue 1/2021
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/s12885-021-09019-5

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