In silico view of MTA1 biochemical signatures in breast malignancy for improvement in immunosurveillance

Metastasis Associated 1 (MTA1) chromatin modifier oncoprotein played a crucial role in both normal and genotoxic stress situations for genome maintenance. To investigates MTA1 regulatory pattern with drug resistance abilities in breast primary carcinoma to advanced invasive stages for identification...

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Main Authors: Zafar Abbas Shah, Humaira Yasmin, Faisal Nouroz, Muhammad Delwar Hussain, Mohsin Kazi
Format: Article
Language:English
Published: Elsevier 2022-04-01
Series:Journal of King Saud University: Science
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S1018364722000246
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author Zafar Abbas Shah
Humaira Yasmin
Faisal Nouroz
Muhammad Delwar Hussain
Mohsin Kazi
author_facet Zafar Abbas Shah
Humaira Yasmin
Faisal Nouroz
Muhammad Delwar Hussain
Mohsin Kazi
author_sort Zafar Abbas Shah
collection DOAJ
description Metastasis Associated 1 (MTA1) chromatin modifier oncoprotein played a crucial role in both normal and genotoxic stress situations for genome maintenance. To investigates MTA1 regulatory pattern with drug resistance abilities in breast primary carcinoma to advanced invasive stages for identification of cancer adapting defense system. We design rationale in silico pipeline from data retrieval to analysis i.e. gene enrichment analysis performed by GeneCards Version 5.1: THE HUMAN GENE DATABASE (www.genecards.org), UALCAN database (www.ualcan.path.uab.edu) for analyzing MTA1 gene expression and promoter methylation in both breasts normal and cancerous tissue samples, cBioPortal for Cancer Genomics (www.cbioportal.org) database for MTA1 mutation analysis and finally analyzed MTA1 functional association with anticancer drugs in breast malignancy via online CCLE GDSC toolkit (www.public.tableau.com/CCLE_GDSC_Correlations). Our results revealed MTA1 overexpression aggressive behavior in stage II, stage III, TNBC-LAR, TNBC-M, TNBC-UNS, IDC, ILC, and post-menopause events of breast malignancy. MTA1 upregulation strongly promotes primary tumor transformation into invasive metastatic carcinoma by hijacking the host lymphatic system and cytokine signaling in both ductal and glandular breast cancers. MTA1 upregulation in the African-American population invites to design de novo model of cancer cell homeostasis under a reduced supply of vegetable nutrients, local-foreign stress, and replicative capacity for metastasis. MTA1 showed a hypomethylation profile that reflects regulatory strength under stress-mediated situations for higher events of transcription. In drug resistance analysis MTA1 has strong resistance towards 15 anti-cancer drugs that confirmed its previously reported behavior of genotoxic stress adaptation for metastasis. Our in silico evidence invites us to design a comprehensive strategy against MTA1 mediated stress managing proteome. In the future there is an urgent need to explore MTA1 shared stress coped protein networks for early diagnosis and better prognosis.
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spelling doaj.art-4aceb697f33d4625a43e4b3413be2eaa2022-12-21T23:40:55ZengElsevierJournal of King Saud University: Science1018-36472022-04-01343101843In silico view of MTA1 biochemical signatures in breast malignancy for improvement in immunosurveillanceZafar Abbas Shah0Humaira Yasmin1Faisal Nouroz2Muhammad Delwar Hussain3Mohsin Kazi4Department of Bioinformatics, Hazara University, Mansehra, PakistanDepartment of Biosciences, COMSATS University Islamabad (CUI), Islamabad, Pakistan; Corresponding authors.Department of Bioinformatics, Hazara University, Mansehra, Pakistan; Corresponding authors.California Health Sciences University, College of Pharmacy, 120 N. Clovis Avenue, Clovis, CA 93612, United StatesDepartment of Pharmaceutics, College of Pharmacy, King Saud University, PO Box 2457, Riyadh 11451, Saudi ArabiaMetastasis Associated 1 (MTA1) chromatin modifier oncoprotein played a crucial role in both normal and genotoxic stress situations for genome maintenance. To investigates MTA1 regulatory pattern with drug resistance abilities in breast primary carcinoma to advanced invasive stages for identification of cancer adapting defense system. We design rationale in silico pipeline from data retrieval to analysis i.e. gene enrichment analysis performed by GeneCards Version 5.1: THE HUMAN GENE DATABASE (www.genecards.org), UALCAN database (www.ualcan.path.uab.edu) for analyzing MTA1 gene expression and promoter methylation in both breasts normal and cancerous tissue samples, cBioPortal for Cancer Genomics (www.cbioportal.org) database for MTA1 mutation analysis and finally analyzed MTA1 functional association with anticancer drugs in breast malignancy via online CCLE GDSC toolkit (www.public.tableau.com/CCLE_GDSC_Correlations). Our results revealed MTA1 overexpression aggressive behavior in stage II, stage III, TNBC-LAR, TNBC-M, TNBC-UNS, IDC, ILC, and post-menopause events of breast malignancy. MTA1 upregulation strongly promotes primary tumor transformation into invasive metastatic carcinoma by hijacking the host lymphatic system and cytokine signaling in both ductal and glandular breast cancers. MTA1 upregulation in the African-American population invites to design de novo model of cancer cell homeostasis under a reduced supply of vegetable nutrients, local-foreign stress, and replicative capacity for metastasis. MTA1 showed a hypomethylation profile that reflects regulatory strength under stress-mediated situations for higher events of transcription. In drug resistance analysis MTA1 has strong resistance towards 15 anti-cancer drugs that confirmed its previously reported behavior of genotoxic stress adaptation for metastasis. Our in silico evidence invites us to design a comprehensive strategy against MTA1 mediated stress managing proteome. In the future there is an urgent need to explore MTA1 shared stress coped protein networks for early diagnosis and better prognosis.http://www.sciencedirect.com/science/article/pii/S1018364722000246MTA1Breast invasive carcinomaGenotoxic stressProliferationDifferentiationApoptotic signaling
spellingShingle Zafar Abbas Shah
Humaira Yasmin
Faisal Nouroz
Muhammad Delwar Hussain
Mohsin Kazi
In silico view of MTA1 biochemical signatures in breast malignancy for improvement in immunosurveillance
Journal of King Saud University: Science
MTA1
Breast invasive carcinoma
Genotoxic stress
Proliferation
Differentiation
Apoptotic signaling
title In silico view of MTA1 biochemical signatures in breast malignancy for improvement in immunosurveillance
title_full In silico view of MTA1 biochemical signatures in breast malignancy for improvement in immunosurveillance
title_fullStr In silico view of MTA1 biochemical signatures in breast malignancy for improvement in immunosurveillance
title_full_unstemmed In silico view of MTA1 biochemical signatures in breast malignancy for improvement in immunosurveillance
title_short In silico view of MTA1 biochemical signatures in breast malignancy for improvement in immunosurveillance
title_sort in silico view of mta1 biochemical signatures in breast malignancy for improvement in immunosurveillance
topic MTA1
Breast invasive carcinoma
Genotoxic stress
Proliferation
Differentiation
Apoptotic signaling
url http://www.sciencedirect.com/science/article/pii/S1018364722000246
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