Genetic variants in m6A modification genes are associated with esophageal squamous-cell carcinoma in the Chinese population

Abstract

<jats:title>Abstract</jats:title> <jats:p>N 6-methyladenosine (m6A) is an abundant modification in RNAs that affects RNA metabolism, and it is reported to be closely related to cancer occurrence and metastasis. In this study, we focused on evaluating the associations between genetic variants in m6A modification genes and the risk of esophageal squamous-cell carcinoma (ESCC). By integrating data of our previous genome-wide association studies and the predictions of several annotation tools, we identified a single nucleotide polymorphism, rs2416282 in the promoter of YTHDC2, that was significantly associated with the susceptibility of ESCC (odds ratio = 0.84, 95% CI: 0.77–0.92, P = 2.81 × 10−4). Through further functional experiments in vitro, we demonstrated that rs2416282 regulated YTHDC2 expression. Knockdown of YTHDC2 substantially promoted the proliferation rate of ESCC cells by affecting several cancer-related signaling pathways. Our results suggested that rs2416282 contributed to ESCC risk by regulating YTHDC2 expression. This study provided us a valuable insight into the roles of genetic variants in m6A modification genes for ESCC susceptibility and may contribute to the prevention of this disease in the future.</jats:p>

Identification and validation of a novel prognostic index based on m6A RNA methylation regulators in esophageal carcinoma

“…Moreover, two clusters of ESCA presented signi cant difference in tumor stage, which also indicated that the expression pattern of these regulators were associated with the malignancy of ESCA. Previously, yang et al reported that genetic variants of m 6 A modi cation genes could affect the ESCA susceptibility [32]. In this study, we also found that genetic alteration of these gene was common in ESCA according to the cBio Cancer Genomics database.…”

Downregulation of m6A reader YTHDC2 promotes tumor progression and predicts poor prognosis in non‐small cell lung cancer

“…Our functional experiments suggested that YTHDC2 could inhibit NSCLC proliferation and migration, which is different to the data reported by Tanabe et al 27 However, our results are consistent with the findings in ESCC. 16 Finally, the prognostic value of YTHDC2 in NSCLC was conducted via online database. Consistent with the conclusions in rectal cancer and head and neck squamous cell carcinoma, the Kaplan-Meier Plotter database validated that low expression of YTHDC2 indicates a poor prognosis in multiple types of cancer, including NSCLC.…”

“…reported that the YTHDC2 gene could be a potential candidate for pancreatic cancer susceptibility and a useful marker of early detection 15 . In addition, loss of YTHDC2 promoted the proliferation rate of esophageal squamous‐cell carcinoma (ESCC) by affecting several cancer‐related signaling pathways 16 . However, whether YTHDC2 is associated with NSCLC remains unknown and needs to be explored further.…”

Role of m6A RNA methylation in cardiovascular disease (Review)

“…SNPs can interfere with m 6 A methylation by altering the RNA sequences of target sites or key flanking nucleotides ( 118 ). Putative m 6 A-related SNPs (m 6 A-SNPs), which are close to or at the exact methylation site, can disrupt m 6 A modification and corresponding biological processes through multiple mechanisms, due to the location of m 6 A-SNPs, and can subsequently affect disease progression ( 119 ). m 6 A-SNPs have been recognized as a fundamental class of crucial multifunctional genetic variants associated with CVDs, which is concerning.…”