In silico identification and in vitro expression analysis of breast cancer-related m6A-SNPs

• Published in: Epigenetics Vol. 17; no. 13; pp. 2144 - 2156
• Main Authors: Kleinbielen, Tamara, Olasagasti, Felix, Azcarate, Daniel, Beristain, Elena, Viguri-Díaz, Amparo, Guerra-Merino, Isabel, García-Orad, África, de Pancorbo, Marian M.
• Format: Journal Article
• Language: English
• Published: Taylor & Francis 09.12.2022; Taylor & Francis Group
• Subjects: A methylation; A-SNP; Breast cancer; epigenetics; m6a methylation; m6a-snp; Research Paper; SNP
• DOI: 10.1080/15592294.2022.2111137
• ISSN: 1559-2294

Research on m 6 A-associated SNPs (m 6 A-SNPs) has emerged recently due to their possible critical roles in many key biological processes. In this sense, several investigations have identified m 6 A-SNPs in different diseases. In order to gain a more complete understanding of the role that m 6 A-SNPs can play in breast cancer, we performed an in silico analysis to identify the m 6 A-SNPs associated with breast cancer and to evaluate their possible effects. For this purpose, we downloaded SNPs related to breast cancer and a list of m 6 A-SNPs from public databases in order to identify which ones appear in both. Subsequently, we assessed the identified m 6 A-SNPs in silico by expression quantitative trait loci (eQTL) analysis and differential gene expression analysis. We genotyped the m 6 A-SNPs found in the in silico analysis in 35 patients with breast cancer, and we carried out a gene expression analysis experimentally on those that showed differences. Our results identified 981 m 6 A-SNPs related to breast cancer. Four m 6 A-SNPs showed an eQTL effect and only three were in genes that presented an altered gene expression. When the three m 6 A-SNPs were evaluated in the tissue sample of our breast cancer patients, only the m 6 A-SNP rs76563149 located in ZNF354A gene presented differences in allele frequencies and a low gene expression in breast cancer tissues, especially in luminal B HER2+ subtype. Future investigations of these m 6 A-SNPs should expand the study in different ethnic groups and increase the sample sizes to test their association with breast cancer and elucidate their molecular function.