Search

Breast cancer is the most common cancer in women both in the developed and less developed countries, and it imposes a considerable threat to human health. Therefore, in order to develop effective targeted therapies against Breast cancer, a deep understanding of its underlying molecular mechanisms is required. The application of deep transcriptional sequencing has been found to be reported to provide an efficient genomic assay to delve into the insights of the diseases and may prove to be useful in the study of Breast cancer. In this study, ChIP-Seq data for normal samples and Breast cancer were compared, and differential peaks identified, based upon fold enrichment (with P-values obtained via t-tests). The Protein-protein interaction (PPI) network analysis was carried out, following which the highly connected genes were screened and studied, and the most promising ones were selected. Biological pathway involved in the process were then identified. Our findings regarding potential Breast cancer-related genes enhances the understanding of the disease and provides prognostic information in addition to standard tumor prognostic factors for future research.

Polycomb group (PcG) proteins have been observed to maintain the pattern of histone by methylation of the histone tail responsible for the gene expression in various cellular processes, of which enhancer of zeste homolog 2 (EZH2) acts as tumor suppressor. Overexpression of EZH2 results in hyper activation found in a variety of cancer. Point mutation on two important residues were induced and the results were compared between the wild type and mutant EZH2. The mutation of Y641 and A677 present in the active region of the protein alters the interaction of the top ranked compound with the newly modeled binding groove of the SET domain, giving a GLIDE score of -12.26 kcal/mol, better than that of the wild type at -11.664 kcal/mol. In depth analysis were carried out for understanding the underlying molecular mechanism using techniques viz. molecular dynamics, principal component analysis, residue interaction network and free energy landscape analysis, which showed that the mutated residues changed the overall conformation of the system along with the residue-residue interaction network. The insight from this study could be of great relevance while designing new compounds for EZH2 enzyme inhibition and the effect of mutation on the overall binding mechanism of the system.