Promoter Methylation-Regulated Differentially Expressed Genes in Breast Cancer

Abstract

Background Breast cancer is one of the most common malignancies among women. Recent studies revealed that differentially methylated regions (DMRs) are implicated in regulating gene expression. The goal of this research was to determine which genes and pathways are dysregulated in breast cancer when their promoters are methylated in an abnormal way, leading to differential expression. Whole-genome bisulfite sequencing was applied to analyze DMRs for eight peripheral blood samples collected from five Saudi females diagnosed with stages I and II of breast cancer aligned with three normal females. Three of those patients and three normal samples were used to determine differentially expressed genes (DEG) using Illumina platform NovaSeq PE150. Results Based on ontology (GO) and KEGG pathways, the analysis indicated that DMGs and DEG are closely related to associated processes, such as ubiquitin-protein transferase activity, ubiquitin-mediated proteolysis, and oxidative phosphorylation. The findings indicated a potentially significant association between global hypomethylation and breast cancer in Saudi patients. Our results revealed 81 differentially promoter-methylated and expressed genes. The most significant differentially methylated and expressed genes found in gene ontology (GO) are pumilio RNA binding family member 1 ( PUM1 ) and zinc finger AN1-type containing 2B ( ZFAND2B ) also known as ( AIRAPL ). Conclusion The essential outcomes of this study suggested that aberrant hypermethylation at crucial genes that have significant parts in the molecular pathways of breast cancer could be used as a potential prognostic biomarker for breast cancer.

Wemics: A Single‐Base Resolution Methylation Quantification Method for Enhanced Prediction of Epigenetic Regulation

“…In addition, most of these Wemics‐detected DMRs in lung cancer were recurrently occurred in other primary cancers from TCGA, suggesting that Wemics‐detected DMRs are not only epigenetically conserved but also highly relevant to tumor development and progression (Figure S8B , Supporting Information). It is well known that tumor suppressor genes often become hyermethylated in cancer, resulting in downregulated gene expression (i.e., Hyper‐Down genes), while oncogenes become hypomethylated in cancer, resulting in upregulated gene expression [ 7 , 35 ] (i.e., Hypo‐Up genes). Therefore, we used the promoter methylation of these Hyper‐Down and Hypo‐Up genes as features to construct a classification model using the random forest algorithm.…”

NORAD-Regulated Signaling Pathways in Breast Cancer Progression

“…PUM expression and its impact on BC is also being debated. Some studies report PUM1 to be one of the most differently expressed and methylated genes in BC [58] and PUM2 to have higher expression in tumors as in TNBC, where it negatively correlates with BC patient overall survival (OS) and relapse-free survival (RFS) [46]. Other studies report lower PUM2 expression in LumA and TNBC tumors compared to normal tissues and that PUM2 silencing increases cell viability, migration and invasion in cancer cells lines, while its OE produces the opposite effect [48].…”