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Exploring the Sirtuin Functionality in Ageing Through Human Protein Interaction Networks

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Abstract

The scientific research of the sirtuin family represents an intriguing topic for the development of therapies of age-related diseases and anti-ageing treatments. The primary aim of the present study is the identification of the signalling and metabolic pathways facilitating the functions of the sirtuin protein interaction network in longevity and age-related diseases. For this reason, increased confidence protein–protein interaction data were collected from the databases BioGRID, HPRD, MINT, and STRING. The pathway enrichment, the gene function prediction, the cluster analysis and the construction of the sirtuin protein interaction network (SPIN) were executed by GeneMania application, which was combined with the protein node prioritization analysis using cyto-Hubba and the cluster analysis application MCODE. The analysis run under the Cytoscape environment was further complemented by the web-based analysis using STRING and DAVID Bioinformatic resources. TGF-β, AR, ER, CARM1, HDAC class I and Notch signalling pathways significantly scored in the pathway enrichment analysis of the extended SPIN. The cluster analysis using MCODE showed the highest score for the interaction network of Notch together with the AR, CARM and ER signalling subnetworks. Additionally, STRING and DAVID Bioinformatic resources tools also emphasized the functions in the sirtuin-mediated viral infections, which represent an emerging topic. The examination of the SPIN by the cyto-Hubba application highlighted HDAC1, EP300, SMAD4, MYC, SIN3A, RBBP4, HDAC2, SIN3B, RBBP7 and SMAD3 as the high-priority essential protein nodes directing the molecular functions of the whole network. The current protein interaction study provides new insights into the sirtuin functions in the longevity and diseases of ageing, which are further discussed in depth.

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Abbreviations

SPIN:

Sirtuin protein interaction network

SPIL:

Sirtuin protein interaction list

TGF-β :

Transforming growth factor β

AR:

Androgen receptor

ER:

Oestrogen receptor

CARM1:

Coactivator associated arginine methyltransferase 1

HDAC:

Histone deacetylase

RB:

Retinoblastoma

MED12:

Mediator of RNA polymerase II transcription

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Acknowledgements

The research was conducted from the financial resources of Biochemworld Co., Uppsala County, Sweden.

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  1. Biochemistry, Molecular, and Cell Biology Unit, Biochemworld co., Snickar-Anders väg 17, 74394, Skyttorp, Uppsala County, Sweden

    Jarmila Nahálková

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Table 1S

The sirtuin protein interaction list (SPIL) and the protein description used in the pathway enrichment and protein function prediction analysis (XLSX 12 kb)

Table 2S

The results of the pathway enrichment analysis using the KEGG pathways analysis of the STRING (v.11) database with FDR value less or equal to 0.05 (XLSX 15 kb)

Table 3S

The results of the pathway enrichment using the Reactome pathways analysis of STRING (v.11) database with FDR value less or equal to 0.05 (XLSX 25 kb)

Table 4S

The results of the pathway enrichment using the KEGG pathways analysis of DAVID Bioinformatic resources (version 6.8), with FDR value less or equal to 0.05 (XLSX 11 kb)

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Nahálková, J. Exploring the Sirtuin Functionality in Ageing Through Human Protein Interaction Networks. SN COMPUT. SCI. 1, 183 (2020). https://doi.org/10.1007/s42979-020-00192-1

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