Research Paper Volume 13, Issue 23 pp 25426—25439
YTHDC1 gene polymorphisms and neuroblastoma susceptibility in Chinese children
- 1 Department of Pediatric Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong, China
- 2 Department of Pediatric Surgery, Hunan Children’s Hospital, Changsha 410004, Hunan, China
- 3 Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, China
- 4 Department of Pediatric Surgery, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning, China
- 5 Department of Pediatric Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China
- 6 Department of Pediatric Surgery, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, Shaanxi, China
- 7 Department of Hematology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325027, Zhejiang, China
- 8 Department of Pathology, Children Hospital and Women Health Center of Shanxi, Taiyuan 030013, Shannxi, China
- 9 Kunming Key Laboratory of Children Infection and Immunity, Yunnan Key Laboratory of Children’s Major Disease Research, Yunnan Institute of Pediatrics Research, Yunnan Medical Center for Pediatric Diseases, Kunming Children’s Hospital, Kunming 650228, Yunnan, China
Received: September 13, 2021 Accepted: December 2, 2021 Published: December 12, 2021
https://doi.org/10.18632/aging.203760How to Cite
Copyright: © 2021 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Neuroblastoma (NB) is the most common extracranial tumor in children. YTHDC1, a member of RNA methylation modification binding proteins, plays critical roles in tumor occurrence and metastasis. However, it is unclear whether YTHDC1 gene polymorphisms are related to NB susceptibility. Herein, we aimed to evaluate the association between YTHDC1 gene polymorphisms (rs2293596 T>C, rs2293595 T>C, rs3813832 T>C) and susceptibility of NB by logistic regression models. In this eight-center case-control study, 898 patients with NB and 1734 healthy controls were genotyped by TaqMan assay. The results showed that rs3813832 TC genotype could significantly reduce the susceptibility of NB compared with the TT genotype [adjusted odds ratio (AOR) = 0.81, 95% confidence interval (CI) = 0.68–0.96, P = 0.018]. Combined genotype analysis revealed that individuals with 3 protective genotypes had a prominently lower NB risk than those with 0-2 protective genotypes (AOR = 0.80, 95% CI = 0.68–0.94, P = 0.006). The stratified analysis also demonstrated the protective effect of rs3813832 TC/CC and 3 protective genotypes in certain subgroups. Further functional experiments revealed that YTHDC1 siRNA-554, targeting the area near the rs3813832 T>C polymorphism site, could observably inhibit the proliferation and migration of NB cells. In conclusion, our findings highlight the involvement of YTHDC1 gene and its genetic variants in the etiology of NB.
Abbreviations
NB: neuroblastoma; GWAS: genome-wide association study; SNP: single nucleotide polymorphism; m6A: N6-methyladenosine; YTHDC1: YTH domain contains protein 1; HWE: Hardy-Weinberg equilibrium; AOR: adjusted odds ratio; CI: confidence interval; UTR: untranslated region; LD: linkage disequilibrium; ATCC: American Type Culture Collection; FBS: fetal bovine serum; ANOVA: analysis of variance.