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Systematically analyses of the common dysregulated networks to understand the common pathologies between T2D and
Zijing Lin1, Fan Yang2, Lijie Sun3
1Department of endocrinology and metabolism, the first affiliated hospital of Harbin Medical University, Harbin, Heilongjiang Province, China.
Background:
Diabetic macroangiopathy, atherosclerosis secondary to diabetes mellitus, causes cerebro-cardiovascular diseases (CVD), which increase the risk of death in patients with DM and significantly reduce their quality of life. Therefore, mechanisms underlying the common shared pathologies between type 2 diabetes (T2D) and atherosclerosis are key to prevention and treatment of diabetic macroangiopathy. However, the common shared pathological links between T2D and atherosclerosis are not fully understood.
Methods:
We constructed a T2D and atherosclerosis associated protein interaction sub-network (TAN) to investigate common shared mechanisms between T2D and atherosclerosis. In addition, MCODE plugin of Cytoscape was applied to TAN to identify most significant functional modules. The network modules were further mapped to KEGG pathway enrichment analysis. Finally, we established a miRNA-gene regulatory network by searching disease associated miRNAs and integrated them into miRNA-gene interaction network for each module.
Results:
TAN contains 1230 nodes which represent the union of T2D and atherosclerosis related genes and 3683 edges which represent the interactions of gene pairs. MCODE plugin was applied and five most significant modular clusters were identified. KEGG analysis of functional modules showed these genes were involved in several pathways including type 2 diabetes mellitus, ErbB and neurotrophin signaling pathway. miRNAgene interaction network was established and these miRNA-gene interactions mediated common shared pathologies between T2D and atherosclerosis.
Conclusions:
Analysis of TAN demonstrated that modular organization of the interaction network elucidates shared pathologies of T2D and atherosclerosis. Furthermore, the disease associated miRNA-gene interaction network enriched our insight into role of miRNAs in mediating common shared pathologies between T2D and atherosclerosis. Thus, miRNAs constitute attractive targets for the development of novel therapies for treating both T2D and atherosclerosis.
Insights
Understanding shared mechanisms between type 2 diabetes (T2D) and atherosclerosis is crucial for treating diabetic macroangiopathy. This study reveals key molecular players and microRNAs (miRNAs) involved in these common pathologies, offering potential therapeutic targets.
Area of Science:
- Biomedical research
- Systems biology
- Genomics
Background:
- Diabetic macroangiopathy, a complication of diabetes mellitus (DM), significantly increases mortality and morbidity due to cerebro-cardiovascular diseases (CVD).
- Atherosclerosis, a key component of diabetic macroangiopathy, shares underlying pathological mechanisms with type 2 diabetes (T2D).
- A comprehensive understanding of these shared pathways is essential for developing effective prevention and treatment strategies for diabetic macroangiopathy, yet these links remain incompletely elucidated.
Purpose of the Study:
- To investigate the common shared mechanisms between type 2 diabetes (T2D) and atherosclerosis.
- To identify key functional modules and pathways implicated in the co-occurrence of T2D and atherosclerosis.
- To explore the role of microRNAs (miRNAs) in mediating these shared pathologies.
Main Methods:
- Construction of a T2D and atherosclerosis associated protein interaction sub-network (TAN) comprising 1230 genes and 3683 interactions.
- Identification of significant functional modules within the TAN using the MCODE plugin in Cytoscape.
- KEGG pathway enrichment analysis of identified modules to determine biological relevance.
- Establishment of a miRNA-gene regulatory network to integrate miRNA involvement in shared pathologies.
Main Results:
- The TAN analysis revealed five significant modular clusters.
- Enriched pathways included type 2 diabetes mellitus, ErbB signaling, and neurotrophin signaling pathways.
- A miRNA-gene interaction network was successfully established, highlighting the role of miRNAs in mediating common pathologies between T2D and atherosclerosis.
Conclusions:
- The modular organization of the protein interaction network elucidates shared pathologies between T2D and atherosclerosis.
- The integrated miRNA-gene network provides novel insights into the function of miRNAs in these interconnected diseases.
- MicroRNAs represent promising therapeutic targets for the development of novel treatments for both T2D and atherosclerosis.
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