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  1. Home
  3. Epigenetic Insights: Unveiling The Impact Of Hypomethylated Cacna2d3 And Flna Genes In Breast Cancer Progression
  1. Home
  3. Epigenetic Insights: Unveiling The Impact Of Hypomethylated Cacna2d3 And Flna Genes In Breast Cancer Progression

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Epigenetic insights: unveiling the impact of hypomethylated CACNA2D3 and FLNA genes in breast cancer progression

Samar Sindi1, Safiah Alhazmi2, Mansour Alsaleem3

  • 1Department of Biological Sciences, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.

Translational Oncology
|July 18, 2025

View abstract on PubMed

Summary
This summary is machine-generated.

DNA hypomethylation influences breast cancer (BC) progression. This study found CACNA2D3 gene hypomethylation and high expression correlate with favorable BC clinicopathological characteristics and prognosis, suggesting its potential as a biomarker.

Keywords:
5-aza-2′-deoxycytidineBreast cancerCACNA2D3DNA methylationMAPK pathwayand FLNA

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Area of Science:

  • Oncology
  • Epigenetics
  • Molecular Biology

Background:

  • Breast cancer (BC) is a leading cause of cancer mortality, driven by genetic and epigenetic changes like DNA hypomethylation.
  • DNA hypomethylation can promote cancer growth, highlighting the need to understand its role in BC progression.

Purpose of the Study:

  • To investigate the expression and methylation status of CACNA2D3 and FLNA genes in breast cancer.
  • To assess the correlation between mRNA expression of these genes and BC clinicopathological characteristics and survival rates.

Main Methods:

  • Whole genome bisulfite sequencing (WGBS) and differentially expressed WGBS (DEGs) were employed to analyze gene expression and methylation.
  • Gene ontology (GO) analysis using WebGestalt identified altered pathways, while public datasets (METABRIC, TCGA) evaluated gene significance.
  • In vitro experiments treated MCF7 and MCF10A cells with 5-aza-2'-deoxycytidine (5-AZA) to study DNA methylation's effect on gene expression.

    • Main Results:

    • CACNA2D3 and FLNA showed significant differences in expression and methylation between BC patients and controls.
    • The MAPK pathway was identified as a significant pathway in BC, with ANGPT1, CACNA2D3, FLNA, and IKBKG as overlapping aberrant hypomethylated genes.
    • CACNA2D3 expression correlated with tumor size, histological grade, and ER/PR status, and increased post-5-AZA treatment, indicating a link to DNA methylation and a favorable prognosis.

    Conclusions:

    • DNA methylation is a potential regulatory factor for CACNA2D3 in breast cancer.
    • High CACNA2D3 expression is associated with specific clinicopathological features and a better prognosis in BC patients.
    • FLNA expression regulation may involve additional factors beyond DNA methylation.