Study of <i>MDM2</i> as Prognostic Biomarker in Brain-LGG Cancer and Bioactive Phytochemicals Inhibit the p53-MDM2 Pathway: A Computational Drug Development Approach
Partha Biswas,
Shabana Bibi,
Qudsia Yousafi,
Asim Mehmood,
Shahzad Saleem,
Awais Ihsan,
Dipta Dey,
Md. Nazmul Hasan Zilani,
Md. Nazmul Hasan,
Rasha Saleem,
Aeshah A. Awaji,
Usama A. Fahmy,
Mohamed M. Abdel-Daim
Affiliations
Partha Biswas
Department of Genetic Engineering and Biotechnology, Faculty of Biological Science and Technology, Jashore University of Science and Technology, Jashore 7408, Bangladesh
Shabana Bibi
Department of Biosciences, Shifa Tameer-e-Millat University, Islamabad 41000, Pakistan
Qudsia Yousafi
Department of Biosciences, Sahiwal Campus, COMSATS University Islamabad, Sahiwal 57000, Pakistan
Asim Mehmood
Department of Biosciences, Sahiwal Campus, COMSATS University Islamabad, Sahiwal 57000, Pakistan
Shahzad Saleem
Department of Biosciences, Sahiwal Campus, COMSATS University Islamabad, Sahiwal 57000, Pakistan
Awais Ihsan
Department of Biosciences, Sahiwal Campus, COMSATS University Islamabad, Sahiwal 57000, Pakistan
Dipta Dey
Biochemistry and Molecular Biology Department, Life Science Faculty, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalgonj 8100, Bangladesh
Md. Nazmul Hasan Zilani
Department of Pharmacy, Faculty of Biological Science and Technology, Jashore University of Science and Technology, Jashore 7408, Bangladesh
Md. Nazmul Hasan
Laboratory of Pharmaceutical Biotechnology and Bioinformatics, Department of Genetic Engineering and Biotechnology, Jashore University of Science and Technology, Jashore 7408, Bangladesh
Rasha Saleem
Department of Laboratory Medicine, Faculty of Applied Medical Sciences, Albaha University, Al Bahah 65431, Saudi Arabia
Aeshah A. Awaji
Department of Biology, Faculty of Science, University College of Taymaa, University of Tabuk, Tabuk 71491, Saudi Arabia
Usama A. Fahmy
Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia
Mohamed M. Abdel-Daim
Department of Pharmaceutical Sciences, Pharmacy Program, Batterjee Medical College, P.O. Box 6231, Jeddah 21442, Saudi Arabia
An evaluation of the expression and predictive significance of the MDM2 gene in brain lower-grade glioma (LGG) cancer was carried out using onco-informatics pipelines. Several transcriptome servers were used to measure the differential expression of the targeted MDM2 gene and search mutations and copy number variations. GENT2, Gene Expression Profiling Interactive Analysis, Onco-Lnc, and PrognoScan were used to figure out the survival rate of LGG cancer patients. The protein–protein interaction networks between MDM2 gene and its co-expressed genes were constructed by Gene-MANIA tool. Identified bioactive phytochemicals were evaluated through molecular docking using Schrödinger Suite Software, with the MDM2 (PDB ID: 1RV1) target. Protein–ligand interactions were observed with key residues of the macromolecular target. A molecular dynamics simulation of the novel bioactive compounds with the targeted protein was performed. Phytochemicals targeting MDM2 protein, such as Taxifolin and (-)-Epicatechin, have been shown with more highly stable results as compared to the control drug, and hence, concluded that phytochemicals with bioactive potential might be alternative therapeutic options for the management of LGG patients. Our once informatics-based designed pipeline has indicated that the MDM2 gene may have been a predictive biomarker for LGG cancer and selected phytochemicals possessed outstanding interaction results within the macromolecular target’s active site after utilizing in silico approaches. In vitro and in vivo experiments are recommended to confirm these outcomes.
