Deciphering the involvement of iron targets in colorectal cancer: a network biology approach

Abstract

Several studies suggested the role of heme iron, but not non-heme iron in colorectal cancer. A network and system biology-based approach was used to understand the role of heme and non-heme iron on colorectal cancer etiology. Heme and non-heme iron targets were screened in addition to CRC targets. The protein-protein interaction map of both iron targets was prepared with CRC targets. Moreover, functional enrichment analysis was performed in order to understand their role in cancer etiology. The heme iron is predicted to modulate several cancer-associated pathways. Our results indicate several targets and pathways, including IL-4/IL-13, ACE, and HIF-1 signaling, that may have an important role in heme iron-mediated CRC and must be given consideration for understanding their role in colorectal cancer.

Keywords: Heme; cancer biology; carcinogenesis; colon cancer; protein-protein interactions; signaling.

Figure 1

Protein-protein interaction map through STRING database for CRC associated heme targets and their direct interactors according to DisGeNet. The protoporphyrin IX (heme) targets are shown with large, blue color nodes, while STRING colors were used for their first neighbors.

Figure 2

The STRING functional enrichment analysis of heme, nonheme targets and their interactors involved in CRC as per DisGeNet. Only top 10 hits are presented in the figure according to FDR value. A. Ferric citrate [nonheme]. B. Ferrous fumarate [nonheme]. C. Protoporphyrin IX [heme].

Figure 3

g:Profiler functional overrepresentation analysis of heme targets and their first neighbors involved in CRC as per DisGeNet. Only top 10 hits (on the basis of adjusted P-value) are presented for enrichment against (A) Gene Ontology:Biological Process, (B) KEGG, (C) REACTOME, and (D) Wikipathways.