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Integrative network-based analysis of mRNA and microRNA expression in 1,25-dihydroxyvitamin D3-treated cancer cells.

Kutmon M, Coort SL, de Nooijer K, Lemmens C, Evelo CT - Genes Nutr (2015)

Bottom Line: Pathway analysis revealed 15 significantly altered pathways: eight more general mostly cell cycle-related pathways and seven cancer-specific pathways.Adding microRNA regulation to the network enabled the identification of gene targets of significantly expressed microRNAs after 1,25(OH)2D3 treatment.Six of the nine differentially expressed microRNAs target genes in the extended network, including CLSPN, an important checkpoint regulator in the cell cycle that was down-regulated, and FZD5, a receptor for Wnt proteins that was up-regulated.

View Article: PubMed Central - PubMed

Affiliation: Department of Bioinformatics - BiGCaT, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University, Maastricht, The Netherlands, martina.kutmon@maastrichtuniversity.nl.

ABSTRACT
Nutritional systems biology is an evolving research field aimed at understanding nutritional processes at a systems level. It is known that the development of cancer can be influenced by the nutritional status, and the link between vitamin D status and different cancer types is widely investigated. In this study, we performed an integrative network-based analysis using a publicly available data set studying the role of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in prostate cancer cells on mRNA and microRNA level. Pathway analysis revealed 15 significantly altered pathways: eight more general mostly cell cycle-related pathways and seven cancer-specific pathways. The changes in the G1-to-S cell cycle pathway showed that 1,25(OH)2D3 down-regulates the genes influencing the G1-to-S phase transition. Moreover, after 1,25(OH)2D3 treatment the gene expression in several cancer-related processes was down-regulated. The more general pathways were merged into one network and then extended with known protein-protein and transcription factor-gene interactions. Network algorithms were used to (1) identify active network modules and (2) integrate microRNA regulation in the network. Adding microRNA regulation to the network enabled the identification of gene targets of significantly expressed microRNAs after 1,25(OH)2D3 treatment. Six of the nine differentially expressed microRNAs target genes in the extended network, including CLSPN, an important checkpoint regulator in the cell cycle that was down-regulated, and FZD5, a receptor for Wnt proteins that was up-regulated. The extendable network-based tools PathVisio and Cytoscape enable straightforward, in-depth and integrative analysis of mRNA and microRNA expression data in 1,25(OH)2D3-treated cancer cells.

No MeSH data available.


Related in: MedlinePlus

Network of interconnected more general pathways. Pathway analysis revealed eight significantly altered more general pathways in 1,25(OH)2D3-treated cancer cells. The pathways were merged into one network using the WikiPathways and BridgeDb apps for Cytoscape. a The fill colours of the nodes in the network indicate their affiliation with one of the more general pathways. Yellow nodes in the network highlight pathway elements linking two or more pathways to each other. b Fourteen genes in the network are up-regulated (red) and 59 genes are down-regulated (blue) in 1,25(OH)2D3-treated cancer cells
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Fig2: Network of interconnected more general pathways. Pathway analysis revealed eight significantly altered more general pathways in 1,25(OH)2D3-treated cancer cells. The pathways were merged into one network using the WikiPathways and BridgeDb apps for Cytoscape. a The fill colours of the nodes in the network indicate their affiliation with one of the more general pathways. Yellow nodes in the network highlight pathway elements linking two or more pathways to each other. b Fourteen genes in the network are up-regulated (red) and 59 genes are down-regulated (blue) in 1,25(OH)2D3-treated cancer cells

Mentions: The 15 altered pathways were grouped in a group of explicitly cancer-related pathways and a group of more general (mostly cell cycle related) pathways (see Table 1). The eight more general pathways were merged into one large network containing 503 nodes and 743 edges (see Fig. 2a). The nodes consist of 319 gene products, 28 metabolites and 15 nodes linking to other pathways. The remaining 141 nodes are used to represent groups and complex interactions.Fig. 2


Integrative network-based analysis of mRNA and microRNA expression in 1,25-dihydroxyvitamin D3-treated cancer cells.

Kutmon M, Coort SL, de Nooijer K, Lemmens C, Evelo CT - Genes Nutr (2015)

Network of interconnected more general pathways. Pathway analysis revealed eight significantly altered more general pathways in 1,25(OH)2D3-treated cancer cells. The pathways were merged into one network using the WikiPathways and BridgeDb apps for Cytoscape. a The fill colours of the nodes in the network indicate their affiliation with one of the more general pathways. Yellow nodes in the network highlight pathway elements linking two or more pathways to each other. b Fourteen genes in the network are up-regulated (red) and 59 genes are down-regulated (blue) in 1,25(OH)2D3-treated cancer cells
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4537452&req=5

Fig2: Network of interconnected more general pathways. Pathway analysis revealed eight significantly altered more general pathways in 1,25(OH)2D3-treated cancer cells. The pathways were merged into one network using the WikiPathways and BridgeDb apps for Cytoscape. a The fill colours of the nodes in the network indicate their affiliation with one of the more general pathways. Yellow nodes in the network highlight pathway elements linking two or more pathways to each other. b Fourteen genes in the network are up-regulated (red) and 59 genes are down-regulated (blue) in 1,25(OH)2D3-treated cancer cells
Mentions: The 15 altered pathways were grouped in a group of explicitly cancer-related pathways and a group of more general (mostly cell cycle related) pathways (see Table 1). The eight more general pathways were merged into one large network containing 503 nodes and 743 edges (see Fig. 2a). The nodes consist of 319 gene products, 28 metabolites and 15 nodes linking to other pathways. The remaining 141 nodes are used to represent groups and complex interactions.Fig. 2

Bottom Line: Pathway analysis revealed 15 significantly altered pathways: eight more general mostly cell cycle-related pathways and seven cancer-specific pathways.Adding microRNA regulation to the network enabled the identification of gene targets of significantly expressed microRNAs after 1,25(OH)2D3 treatment.Six of the nine differentially expressed microRNAs target genes in the extended network, including CLSPN, an important checkpoint regulator in the cell cycle that was down-regulated, and FZD5, a receptor for Wnt proteins that was up-regulated.

View Article: PubMed Central - PubMed

Affiliation: Department of Bioinformatics - BiGCaT, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University, Maastricht, The Netherlands, martina.kutmon@maastrichtuniversity.nl.

ABSTRACT
Nutritional systems biology is an evolving research field aimed at understanding nutritional processes at a systems level. It is known that the development of cancer can be influenced by the nutritional status, and the link between vitamin D status and different cancer types is widely investigated. In this study, we performed an integrative network-based analysis using a publicly available data set studying the role of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in prostate cancer cells on mRNA and microRNA level. Pathway analysis revealed 15 significantly altered pathways: eight more general mostly cell cycle-related pathways and seven cancer-specific pathways. The changes in the G1-to-S cell cycle pathway showed that 1,25(OH)2D3 down-regulates the genes influencing the G1-to-S phase transition. Moreover, after 1,25(OH)2D3 treatment the gene expression in several cancer-related processes was down-regulated. The more general pathways were merged into one network and then extended with known protein-protein and transcription factor-gene interactions. Network algorithms were used to (1) identify active network modules and (2) integrate microRNA regulation in the network. Adding microRNA regulation to the network enabled the identification of gene targets of significantly expressed microRNAs after 1,25(OH)2D3 treatment. Six of the nine differentially expressed microRNAs target genes in the extended network, including CLSPN, an important checkpoint regulator in the cell cycle that was down-regulated, and FZD5, a receptor for Wnt proteins that was up-regulated. The extendable network-based tools PathVisio and Cytoscape enable straightforward, in-depth and integrative analysis of mRNA and microRNA expression data in 1,25(OH)2D3-treated cancer cells.

No MeSH data available.


Related in: MedlinePlus