Association Between Nuclear Receptor Coactivator 1 and Stem Cell Signaling Pathway and Identification of Natural NCOA1 Inhibitors: An in-silico Study
Nuclear receptor coactivator 1 (NCOA1) is overexpressed in various cancer and is associated with disease resistance and its poor prognosis. miRNAs are the short stretch of noncoding nucleotide sequence responsible for RNA silencing and post-transcriptional gene regulation. Deregulated expression of miRNAs is associated with carcinogenesis. Present study focuses on the evolution of the NCOA1, identification of miRNAs (and their associated pathways) occupied in the regulation of NCOA1, and natural inhibitors of the protein by using various online and offline computational tools such as, molecular evolutionary genetics analysis (MEGA6) tool, DIANA-mirPathv3 software and Maestro 9.6 (Schrödinger Inc) respectively. The phylogenetic analyses of different isolates of nuclear receptor coactivator show that humans formed a separate clade. Five miRNAs (has-mir-186-3p, has-mir-27a-3p, has-mir-27b-3p, has-mir-7-2-3p, and has-mir-374a-5p) occupied in the regulation of NCOA1 protein were found to highly associated with cancer stem cell pathway. Excellent Dock Score of kaempferol and hesperidin analogs was found against NCOA1 active site. The interactions pattern underlined the involvement of lipophilic, electrostatic, hydrogen bonding, π-cation stacking, and π-π stacking mode of interaction at the active site. Thus analog of kaempferol and hesperidin may contribute to developing as a potential agent for cancer chemotherapy and resistance. Association of recognized miRNAs with NCOA1 protein strengthens its role in cancer resistance through stem cell signaling pathways.
KeywordNuclear receptor coactivator 1 Cancer Phylogenetic tree Natural compounds Maestro 9.6 Pathway prediction
PS and PPK acknowledge Indian Council of Medical Research (ICMR), India and UGC-CSIR, India respectively for providing the financial assistance in the form of Postdoc and Junior Research Fellowship. SK acknowledges the Central University of Punjab for providing infrastructure facilities.
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