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

Cited by 10 publications

(10 citation statements)

References 33 publications

(34 reference statements)

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“…In molecular docking, the ligand binds to one or more amino acid residues with hydrogen bonds in the active pocket, and participates in the process of conformational changes and energy complementation. 29 The binding sites and binding score values can intuitively reflect the interaction and stability of the docking model. Here, we select the first 15 targets with higher DOF (except for receptors lacking the original ligand in the PDB) to construct protein receptors based on hub targets of PPI.…”

Section: Resultsmentioning

confidence: 99%

Exploring the potential therapeutic effect of Eucommia ulmoides–Dipsaci Radix herbal pair on osteoporosis based on network pharmacology and molecular docking technology

et al. 2022

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Section: Resultsmentioning

confidence: 99%

Exploring the potential therapeutic effect of Eucommia ulmoides–Dipsaci Radix herbal pair on osteoporosis based on network pharmacology and molecular docking technology

et al. 2022

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“…A previous study showed that these two pathways were enriched in DEGs both in the GSE32018 and GSE9327 datasets, which used normal and reactive lymph nodes as controls, respectively (22). This indicates that the enriched pathways in DEGs between tumor samples and controls might be a reason for the selection of targeted agents in MCL, such as bortezomib interfering with the NF-kappa B signaling pathway (1).…”

Section: Discussionmentioning

confidence: 98%

Identification of immune-related genes and development of a prognostic model in mantle cell lymphoma

Zhang¹,

Shi²,

Wang³

et al. 2022

Ann Transl Med

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Background: The immune landscape, prognostic model, and molecular variations of mantle cell lymphoma (MCL) remain unclear. Hence, an integrated bioinformatics analysis of MCL datasets is required for the development of immunotherapy and the optimization of targeted therapies.Methods: Data were obtained from the Gene Expression Omnibus (GEO) database (GSE32018, GSE45717 and GSE93291). The differentially expressed immune-related genes were selected, and the hub genes were screened by three machine learning algorithms, followed by enrichment and correlation analyses. Next, MCL molecular clusters based on the hub genes were identified by K-Means clustering, the probably approximately correct (PAC) algorithm, and principal component analysis (PCA). The landscape of immune cell infiltration and immune checkpoint molecules in distinct clusters was explored by single-sample gene-set enrichment analysis (ssGSEA) as well as the CIBERSORT and xCell algorithms. The prognostic genes and prognostic risk score model for MCL clusters were identified by least absolute shrinkage and selection operator (LASSO)-Cox analysis and cross-validation for lambda. Correlation analysis was performed to explore the correlation between the screened prognostic genes and immune cells or immune checkpoint molecules.Results: Four immune-related hub genes (CD247, CD3E, CD4, and GATA3) were screened in MCL, mainly enriched in the T-cell receptor signaling pathway. Based on the hub genes, two MCL molecular clusters were recognized. The cluster 2 group had a significantly worse overall survival (OS), with downregulated hub genes, and a variety of activated immune effector cells declined. The majority of immune checkpoint molecules had also decreased. An efficient prognostic model was established, including six prognostic genes (LGALS2, LAMP3, ICOS, FCAMR, IGFBP4, and C1QA) differentially expressed between two MCL clusters. Patients with a higher risk score in the prognostic model had a poor prognosis.Furthermore, most types of immune cells and a range of immune checkpoint molecules were positively correlated with the prognostic genes.Conclusions: Our study identified distinct molecular clusters based on the immune-related hub genes, and showed that the prognostic model affected the prognosis of MCL patients. These hub genes, modulated immune cells, and immune checkpoint molecules might be involved in oncogenesis and could be potential prognostic biomarkers in MCL.

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“…In the literature the proteolytic cleavage of E-cad was reported for a number of sheddases, including zinc-dependent matrix metalloproteinases (MMP-2, -3, -7, -9 and -14), members of the disintegrin family (adamalysin/ADAM-10 and−15), bacterial proteases gingipains (HRgpA, RgpB, and Kgp), B. fragilis toxin/fragilysin, cysteine cathepsins (B, L, and S), serine protease Kallikrein-7 (KLK7), plasmin serine protease, aspartic proteinases BACE1 and BACE2, and malaria parasite serine proteinases PfSUB2n, PfROM1, and PfROM 4 (Grabowska and Day, 2012). One possible candidate for E-cad cleavage during C. burnetii infections could be the human MMP-9, since: (i) MMP-9 levels were reported elevated in the sera of patients with endocarditis (Thuny et al, 2012), and patients with acute Q fever (Krajinović et al, 2012); (ii) its production was induced in PBMCs of healthy persons following in vitro exposure to C. burnetii ; (iii) MMP-9 SNP was found more frequently in patients with persistent Q fever (Jansen et al, 2017); and (iv) MMP-9 was recently identified as a key gene in mantle cell lymphoma (Yan et al, 2018). Experiments are under progress in our laboratory to investigate whether C. burnetii infection induces the activation of a human cellular protease from the sheddase family or if C. burnetii itself encodes for a sheddase.…”

Section: Discussionmentioning

confidence: 99%

High Concentrations of Serum Soluble E-Cadherin in Patients With Q Fever

Mezouar

Osman

Melenotte

et al. 2019

Front. Cell. Infect. Microbiol.

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Cadherins switching is a hallmark of neoplasic processes. The E-cadherin (E-cad) subtype is one of the surface molecules regulating cell-to-cell adhesion. After its cleavage by sheddases, a soluble fragment (sE-cad) is released that has been identified as a pro-carcinogenic inflammatory signal in several bacteria-induced cancers. Recently we reported that Q fever, a disease due to Coxiella burnetii infection, can be complicated by occurrence of non-Hodgkin lymphoma (NHL). Therefore, we studied E-cad switching in Q fever. The sE-cad levels were found increased in the sera of acute and persistent Q fever patients, whereas they remained at the baseline in controls groups of healthy donors, people cured of Q fever, patients suffering from unrelated inflammatory diseases, and past Q fever patients who developed NHL. These results indicate that sE-cad can be considered as a new biomarker of C. burnetii infection rather than a marker of NHL-associated to Q fever. We wondered if changes in sE-cad reflected variations in the CDH1 gene transcription. The expression of E-cad mRNA and its intracellular ligand β-catenin was down-regulated in peripheral blood mononuclear cells (PBMCs) of patients with either acute or persistent forms of Q fever. Indeed, a lower cell-surface expression of E-cad was measured in a minority (<5%) subpopulation of HLADR + /CD16 + monocytes from patients with acute Q fever. However, a very strong increase in E-cad expression was observed on more than 30% of the HLADR + /CD16 + monocytes of persistent Q fever patients, a cell subpopulation known to be a target for C. burnetii in humans. An experimental in vitro infection of healthy donors' PBMCs with C. burnetii , was performed to directly evaluate the link between C. burnetii interaction with PBMCs and their E-cad expression. A significant increase in the percentage of HLADR + /CD16 + monocytes expressing E-cad was measured after PBMCs had been incubated for 8 h with C. burnetii Nine Mile strain. Altogether, these data demonstrate that C. burnetii severely impairs the E-cad expression in circulating cells of Q fever patients.

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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

Cited by 10 publications

References 33 publications

Exploring the potential therapeutic effect of Eucommia ulmoides–Dipsaci Radix herbal pair on osteoporosis based on network pharmacology and molecular docking technology

Exploring the potential therapeutic effect of Eucommia ulmoides–Dipsaci Radix herbal pair on osteoporosis based on network pharmacology and molecular docking technology

Identification of immune-related genes and development of a prognostic model in mantle cell lymphoma

High Concentrations of Serum Soluble E-Cadherin in Patients With Q Fever

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