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.
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Acknowledgements
This research was supported by Science and Engineering Research Board (SERB), Department of Science and Technology (DST), Govt. of India (sanction order No. “ECR/2016/000965”).
Funding
The author, Dr. Koustav Sarkar is extremely thankful for the financial help for the DST-SERB project of the Department of Science and Technology, India (Ref. No. ECR/2016/000965, Date: 20.02.2017).
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SR: data curation, formal analysis, methodology, and software, and writing—original draft preparation, MG: resources and supervision, LEH: resources and supervision, JSS: software and formal analysis, KVL: resources, KS: conceptualization, supervision, visualization, resources, and writing—review and editing.
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Ethical approval was obtained from Institutional Ethics Committee of SRM Medical College Hospital and Research Centre, Kattankulathur, Tamil Nadu 603204, India.
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432_2022_4130_MOESM1_ESM.tif
Supplementary file1 (TIF 2086 KB) Highest clustered gene–gene interaction network of dysregulated genes from IDC disease data set
432_2022_4130_MOESM2_ESM.tif
Supplementary file2 (TIF 1658 KB) Highest clustered gene–gene interaction network of dysregulated genes from CAD disease data set
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Rakshit, S., Sunny, J.S., George, M. et al. 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 148, 3421–3436 (2022). https://doi.org/10.1007/s00432-022-04130-x
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DOI: https://doi.org/10.1007/s00432-022-04130-x