Deciphering crucial genes in multiple sclerosis pathogenesis and drug repurposing: A systems biology approach

Dadashkhan, Sadaf; Mirmotalebi, Seyed Amir; Sameni, Marzie; Ghani, Sepideh; Poursheykhi, Hossein; Abbasi, Maryam; Kalantari, Sima; Zali, Hakimeh

doi:10.1016/j.jprot.2023.104890

Cited by 6 publications

(3 citation statements)

References 82 publications

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“…In recent decades, systems biology approaches, such as protein-protein interaction (PPI) and gene regulatory network (GRN) analyses, have revolutionized the understanding of molecular mechanisms underlying biological phenomena and pathologies [ 12 ]. These innovative approaches have been instrumental in unraveling the intricate molecular connections and relationships among various diseases [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Deciphering molecular bridges: Unveiling the interplay between metabolic syndrome and Alzheimer’s disease through a systems biology approach and drug repurposing

Azizan,

Zali,

Mirmotalebisohi

et al. 2024

PLoS ONE

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The association between Alzheimer’s disease and metabolic disorders as significant risk factors is widely acknowledged. However, the intricate molecular mechanism intertwining these conditions remains elusive. To address this knowledge gap, we conducted a thorough investigation using a bioinformatics method to illuminate the molecular connections and pathways that provide novel perspectives on these disorders’ pathological and clinical features. Microarray datasets (GSE5281, GSE122063) from the Gene Expression Omnibus (GEO) database facilitated the way to identify genes with differential expression in Alzheimer’s disease (141 genes). Leveraging CoreMine, CTD, and Gene Card databases, we extracted genes associated with metabolic conditions, including hypertension, non-alcoholic fatty liver disease, and diabetes. Subsequent analysis uncovered overlapping genes implicated in metabolic conditions and Alzheimer’s disease, revealing shared molecular links. We utilized String and HIPPIE databases to visualize these shared genes’ protein-protein interactions (PPI) and constructed a PPI network using Cytoscape and MCODE plugin. SPP1, CD44, IGF1, and FLT1 were identified as crucial molecules in the main cluster of Alzheimer’s disease and metabolic syndrome. Enrichment analysis by the DAVID dataset was employed and highlighted the SPP1 as a novel target, with its receptor CD44 playing a significant role in the inflammatory cascade and disruption of insulin signaling, contributing to the neurodegenerative aspects of Alzheimer’s disease. ECM-receptor interactions, focal adhesion, and the PI3K/Akt pathways may all mediate these effects. Additionally, we investigated potential medications by repurposing the molecular links using the DGIdb database, revealing Tacrolimus and Calcitonin as promising candidates, particularly since they possess binding sites on the SPP1 molecule. In conclusion, our study unveils crucial molecular bridges between metabolic syndrome and AD, providing insights into their pathophysiology for therapeutic interventions.

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Section: Introductionmentioning

confidence: 99%

Deciphering molecular bridges: Unveiling the interplay between metabolic syndrome and Alzheimer’s disease through a systems biology approach and drug repurposing

Azizan,

Zali,

Mirmotalebisohi

et al. 2024

PLoS ONE

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“…Several research studies have used different systems biology approaches, including protein–protein interaction (PPI) network analysis and gene regulatory networks (GRNs), to decipher the molecular pathology behind various illnesses and conditions. 5 , 6 , 7 , 8 Some research has stated that GRN disruption is related to developing various diseases, including GBM. 9 , 10 Besides, studies have demonstrated a role for both protein‐coding and non‐coding RNAs (ncRNA) in aberrant gene expression and GBM progression 11 , 12 , 13 ; However, their regulatory relationships and functions are still largely unknown.…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Comprehensive analysis of lncRNA‐associated ceRNA network reveals novel potential prognostic regulatory axes in glioblastoma multiforme

Bazrgar,

Mirmotalebisohi,

Ahmadi

et al. 2024

J Cellular Molecular Medi

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Deciphering the lncRNA‐associated competitive endogenous RNA (ceRNA) network is essential in decoding glioblastoma multiforme (GBM) pathogenesis by regulating miRNA availability and controlling mRNA stability. This study aimed to explore novel biomarkers for GBM by constructing a lncRNA‐miRNA‐mRNA network. A ceRNA network in GBM was constructed using lncRNA, mRNA and miRNA expression profiles from the TCGA and GEO datasets. Seed nodes were identified by protein–protein interaction (PPI) network analysis of deregulated‐mRNAs (DEmRNAs) in the ceRNA network. A lncRNA‐miRNA‐seed network was constructed by mapping the seed nodes into the preliminary ceRNA network. The impact of the seed nodes on the overall survival (OS) of patients was assessed by the GSCA database. Functional enrichment analysis of the deregulated‐lncRNAs (DElncRNA) in the ceRNA network and genes interacting with OS‐related genes in the PPI network were performed. Finally, the positive correlation between seed nodes and their associated lncRNAs and the expression level of these molecules in GBM tissue compared with normal samples was validated using the GEPIA database. Our analyzes revealed that three novel regulatory axes AL161785.1/miR‐139‐5p/MS4A6A, LINC02611/miR‐139‐5p/MS4A6A and PCED1B‐AS1/miR‐433‐3p/MS4A6A may play essential roles in GBM pathogenesis. MS4A6A is upregulated in GBM and closely associated with shorter survival time of patients. We also identified that MS4A6A expression positively correlates with genes related to tumour‐associated macrophages, which induce macrophage infiltration and immune suppression. The functional enrichment analysis demonstrated that DElncRNAs are mainly involved in neuroactive ligand–receptor interaction, calcium/MAPK signalling pathway, ribosome, GABAergic/Serotonergic/Glutamatergic synapse and immune system process. In addition, genes related to MS4A6A contribute to immune and inflammatory‐related biological processes. Our findings provide novel insights to understand the ceRNA regulation in GBM and identify novel prognostic biomarkers or therapeutic targets.

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COVID-19: A novel holistic systems biology approach to predict its molecular mechanisms (in vitro) and repurpose drugs

Sameni,

Mirmotalebisohi,

Dadashkhan

et al. 2023

DARU J Pharm Sci

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Deciphering crucial genes in multiple sclerosis pathogenesis and drug repurposing: A systems biology approach

Cited by 6 publications

References 82 publications

Deciphering molecular bridges: Unveiling the interplay between metabolic syndrome and Alzheimer’s disease through a systems biology approach and drug repurposing

Deciphering molecular bridges: Unveiling the interplay between metabolic syndrome and Alzheimer’s disease through a systems biology approach and drug repurposing

Comprehensive analysis of lncRNA‐associated ceRNA network reveals novel potential prognostic regulatory axes in glioblastoma multiforme

COVID-19: A novel holistic systems biology approach to predict its molecular mechanisms (in vitro) and repurpose drugs

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