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

• Published in: Journal of cancer research and clinical oncology 2022-12, Vol.148 (12), p.3421-3436
• Main Authors: Rakshit, Sudeshna, Sunny, Jithin S., George, Melvin, Hanna, Luke Elizabeth, Leela, K. V., Sarkar, Koustav
• Format: Article
• Language: English
• Subjects: BRCA1 protein; Breast cancer; Cancer Research; Cardiovascular disease; CD4 antigen; Coronary artery; Coronary vessels; CRISPR; Cytotoxicity; DNA damage; DNA methylation; Epigenetics; Heart diseases; Helper cells; Hematology; Inflammation; Internal Medicine; Invasiveness; L-Lactate dehydrogenase; Lactic acid; Lymphocytes T; Medicine; Medicine & Public Health; N6-methyladenosine; Oncology; Original Article – Cancer Research; p53 Protein; Polymerase chain reaction; Ribonucleic acid; Risk factors; RNA; Signal transduction; Tumor suppressor genes; Tumors; Vein & artery diseases
• ISSN: 0171-5216; 1432-1335
• DOI: 10.1007/s00432-022-04130-x

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.