Dataset Information

Genome-wide identification of m6A-associated functional SNPs as potential functional variants for thyroid cancer.

ABSTRACT: m6A methylation has been demonstrated to be one of the most important epigenetic regulation mechanisms in cell differentiation and cancer development especially m6A derived diagnostic and prognostic biomarkers have been identified in the past several years. However, systemic investigation to the interaction between germline single-nucleotide polymorphisms (SNPs) and m6A has not been conducted yet. In this study, we collected previous identified significant thyroid cancer associated SNPs from UKB cohort (358 cases and 407,399 controls) and ICR cohort (3,001 patients and 287,550 controls) and thyroid eQTL (sample size = 574 from GTEx project) and m6A-SNP (N = 1,678,126) were applied to prioritize the candidate SNPs. Finally, five candidate genes (PLEKHA8, SMUG1, CDC123, RMI2, ACSM5) were identified to be thyroid cancer associated m6A-related genetic susceptibility. Loss and gain function studies of m6A writer proteins confirm that ACSM5 is regulated by m6A methylation of mRNA. Moreover, ACSM5 is downregulated in thyroid cancer and inversely correlated with PTC malignancy and patient survival. Together, our study highlight mRNA-seq and m6A-seq double analysis provided a novel approach to identify cancer biomarkers and understanding the heterogeneity of human cancers.

SUBMITTER: Ruan X

PROVIDER: S-EPMC8640822 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Genome-wide identification of m6A-associated functional SNPs as potential functional variants for thyroid cancer.

Ruan Xianhui X Tian Mengran M Kang Ning N Ma Weike W Zeng Yu Y Zhuang Gaojian G Zhang Wei W Xu Guangwei G Hu Linfei L Hou Xiukun X Xie Wenjun W Gao Ming M Piao Yongjun Y Guo Shicheng S Zheng Xiangqian X

American journal of cancer research 20211115 11

m6A methylation has been demonstrated to be one of the most important epigenetic regulation mechanisms in cell differentiation and cancer development especially m6A derived diagnostic and prognostic biomarkers have been identified in the past several years. However, systemic investigation to the interaction between germline single-nucleotide polymorphisms (SNPs) and m6A has not been conducted yet. In this study, we collected previous identified significant thyroid cancer associated SNPs from UKB ...[more]

PMID: 34873468

Similar Datasets

Project description:ObjectivesN6-methyladenosine (m6A) is essential in the regulation of the immune system, but the role that its single nucleotide polymorphisms (SNPs) play in the pathogenesis of type 1 diabetes (T1D) remains unknown. This study demonstrated the association between genetic variants in m6A regulators and T1D risk based on a case-control study in a Chinese population.MethodsThe tagging SNPs in m6A regulators were genotyped in 1005 autoantibody-positive patients with T1D and 1257 controls using the Illumina Human OmniZhongHua-8 platform. Islet-specific autoantibodies were examined by radioimmunoprecipitation in all the patients. The mixed-meal glucose tolerance test was performed on 355 newly diagnosed patients to evaluate their residual islet function. The functional annotations for the identified SNPs were performed in silico. Using 102 samples from a whole-genome expression microarray, key signaling pathways associated with m6A regulators in T1D were comprehendingly evaluated.ResultsUnder the additive model, we observed three tag SNPs in the noncoding region of the PRRC2A (rs2260051, rs3130623) and YTHDC2 (rs1862315) gene are associated with T1D risk. Although no association was found between these SNPs and islet function, patients carrying risk variants had a higher positive rate for ZnT8A, GADA, and IA-2A. Further analyses showed that rs2260051[T] was associated with increased expression of PRRC2A mRNA (P = 7.0E-13), and PRRC2A mRNA was significantly higher in peripheral blood mononuclear cell samples from patients with T1D compared to normal samples (P = 0.022). Enrichment analyses indicated that increased PRRC2A expression engages in the most significant hallmarks of cytokine-cytokine receptor interaction, cell adhesion and chemotaxis, and neurotransmitter regulation pathways. The potential role of increased PRRC2A in disrupting immune homeostasis is through the PI3K/AKT pathway and neuro-immune interactions.ConclusionThis study found intronic variants in PRRC2A and YTHDC2 associated with T1D risk in a Chinese Han population. PRRC2A rs2260051[T] may be implicated in unbalanced immune homeostasis by affecting the expression of PRRC2A mRNA. These findings enriched our understanding of m6A regulators and their intronic SNPs that underlie the pathogenesis of T1D.

Dataset Information

Genome-wide identification of m6A-associated functional SNPs as potential functional variants for thyroid cancer.

Publications

Genome-wide identification of m6A-associated functional SNPs as potential functional variants for thyroid cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets