2026-10-12T06:06:34Z https://api.figshare.com/v2/oai

oai:figshare.com:article/33941884 2026-09-19T08:31:36Z category_7 portal_147 item_type_3 month_year_09_2026

Supplemental Material for: Epigenetic and Transcriptional Dysregulation of Ribosomal Genes in Esophageal Adenocarcinoma: A Multi-omics Mendelian Randomization Study figshare admin karger (2628495) Yushan Chen (510334) Cuiyan Zheng (25075426) Lingling Huang (1429468) Hongwei Huang (1444249) Yong Lin (177139) Shaoqiang Chen (6598439) Medicine Medicine <p dir="ltr">Introduction: The rising incidence and poor prognosis of esophageal adenocarcinoma (EAC) highlight the urgent need to identify novel molecular determinants. Ribosome heterogeneity has emerged as a potential factor in carcinogenesis, yet its causal relevance in EAC remains unclear. We aimed to systematically evaluate the causal effects of ribosome-related genes on EAC risk by integrating multi-omics data.</p><p dir="ltr">Methods: We applied summary-data-based Mendelian randomization (SMR) to analyze 1,329 ribosome-related genes, integrating mQTL, eQTL, pQTL data and a large EAC GWAS. Bayesian colocalization and esophageal tissue transcriptome analyses validated causal signals. We compared mRNA/protein levels of candidate genes in normal HET-1A esophageal cells versus EAC cell lines OE33 and OE19, and validated methylation-gene correlations using the TCGA-ESCA cohort. Crucially, functional assays, including CCK-8, Transwell, colony formation, and apoptosis assays, were performed in OE33 cells following gene overexpression to verify their causal roles.</p><p dir="ltr">Results: SMR analyses identified EIF2B2 and RPS6KL1 as causal protective genes for EAC; genetically elevated expression of both reduced EAC risk. A regulatory cascade was uncovered, whereby specific CpG methylation repressed gene transcription to alter disease susceptibility. Consistently, EIF2B2 and RPS6KL1 mRNA and protein were markedly lower in OE33/OE19 tumor cells than HET-1A. TCGA data confirmed negative correlation between RPS6KL1 promoter cg19899223 methylation and gene expression (ρ = -0.27, p = 0.00015). Functionally, overexpression of EIF2B2 and RPS6KL1 in OE33 cells significantly suppressed cell viability, invasion, and colony formation, while inducing apoptosis, thereby experimentally validating their tumor-suppressive effects.</p><p dir="ltr">Conclusion: By integrating multi-omics evidence with functional assays, this study identifies EIF2B2 and RPS6KL1 as causal protective factors in EAC etiology. These findings suggest that maintaining ribosomal homeostasis via these genes acts as a barrier against EAC, highlighting their potential for risk stratification and therapeutic targeting.</p> 2026-09-19T08:31:36Z Dataset Dataset 10.6084/m9.figshare.33941884.v1 https://figshare.com/articles/dataset/Supplemental_Material_for_Epigenetic_and_Transcriptional_Dysregulation_of_Ribosomal_Genes_in_Esophageal_Adenocarcinoma_A_Multi-omics_Mendelian_Randomization_Study/33941884 CC BY 4.0