Identification of MMP9 as a novel key gene in mantle cell lymphoma based on bioinformatic analysis and design of cyclic peptides as MMP9 inhibitors based on molecular docking

Yan,Wei; Li,Shawn Xiang; Wei,Minjie; Gao,Hua

doi:10.3892/or.2018.6682

Identification of MMP9 as a novel key gene in mantle cell lymphoma based on bioinformatic analysis and design of cyclic peptides as MMP9 inhibitors based on molecular docking

Authors:
- Wei Yan
- Shawn Xiang Li
- Minjie Wei
- Hua Gao
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Affiliations: Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, Liaoning 110122, P.R. China, International College, China Medical University, Shenyang, Liaoning 110122, P.R. China, Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, Liaoning 110122, P.R. China
Published online on: September 5, 2018 https://doi.org/10.3892/or.2018.6682
Pages: 2515-2524
Copyright: © Yan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Mantle cell lymphoma (MCL) is an aggressive disease. MCL is associated with poor patient prognosis and limited survival. To identify key genes and explore targeting cyclic peptide inhibitors for the treatment of MCL, we downloaded two gene expression profiles (GSE32018 and GSE9327) from the Gene Expression Omnibus (GEO) database. We screened 84 differentially expressed genes (DEGs). Pathway analysis showed that DEMs were mainly enriched in the ʻPathway in cancerʼ, ʻPI3K‑Akt signaling pathwayʼ, ʻCytokine‑cytokine receptor interactionʼ, ʻRap1 signaling pathwayʼ, ʻNF‑κB signaling pathwayʼ and ʻLeukocyte trans‑endothelial migrationʼ. We subsequently constructed a protein‑protein interaction (PPI) network of DEGs. In addition, matrix metalloproteinase 9 (MMP9) with a high degree in the PPI network was identified as a hub gene in MCL. Meanwhile in the Molecular Complex Detection (MCODE) analysis, MMP9 was located in the important cluster. Thus, MMP9 can be used as a therapeutic target for MCL and we designed cyclic peptides as MMP9 inhibitors. MMP9 protein structure was gathered from the Protein Data Bank (PDB), with a PDB ID: 1L6J. MMP9 and cyclic peptides were docked using Molecular Operating Environment (MOE) software after structural optimization. It was revealed that cyclic peptide 2 bound deeply in the binding pocket of MMP9 and had interaction with the active‑site Zn2+ ion in the catalytic domain. Cyclic peptides 1, 2, 4‑6 also displayed potential interaction with active residues of MMP9; thus, these cyclic peptides can serve as potential drug candidates to block MMP9 activity and future studies are warranted to confirm their efficacy.

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