T helper cell-mediated epitranscriptomic regulation via m6A RNA methylation bridges link between coronary artery disease and invasive ductal carcinoma

J Cancer Res Clin Oncol. 2022 Dec;148(12):3421-3436. doi: 10.1007/s00432-022-04130-x. Epub 2022 Jul 1.

Abstract

Purpose: Invasive ductal carcinoma (IDC) and coronary artery disease (CAD), remains the greatest cause of death annually in women, driven by complex signalling pathways and shared several predisposing risk factors together. Therefore, it is important to find out the common epigenetic modifications which are responsible for possible disease progression from CAD to IDC.

Methods: CD4+T cell isolation by MACS, RT2 profiler PCR array, Gene ontology study, m6A RNA methylation, ChIP-qPCR, Q-PCR, CRISPR/Cas9-mediated knockout/overexpression, Lactate dehydrogenase release assay, RDIP-qPCR.

Results: We have identified several epigenetic regulators (e.g., VEGFA, AIMP1, etc.) which are mainly involved in inflammatory pathways in both the diseased conditions. Epitranscriptomic alterations such as m6A RNA methylation found abnormal in CD4+T helper cells in both IDC as well as CAD. CRISPR-Cas9 mediated knockout/overexpression of specific gene (BRCA1) are promising therapeutic approaches in diseased conditions by regulating m6A RNA methylation and also tumor suppressor gene P53. It also affected the R-loop formation which is vulnerable to DNA damage and BRCA1 can also induce CTL mediated cytotoxicity in breast cancer cells.

Conclusions: Therefore, by understanding the modifications of epigenetic mechanisms, their alterations and interactions will aid in the development of newer therapeutic approaches to stop the possible spread from one disease to another.

Keywords: AIMP1; BRCA1; Inflammation; P53; R-loop; VEGFA.

MeSH terms

  • Carcinoma, Ductal*
  • Coronary Artery Disease* / genetics
  • Female
  • Humans
  • Lactate Dehydrogenases
  • Methylation
  • RNA / genetics
  • T-Lymphocytes, Helper-Inducer
  • Tumor Suppressor Protein p53

Substances

  • Tumor Suppressor Protein p53
  • RNA
  • Lactate Dehydrogenases