Identification of the C-Reactive Protein Interaction Network Using a Bioinformatics Approach Provides Insights into the Molecular Pathogenesis of Hepatocellular Carcinoma.

Abstract

BACKGROUND/AIMS:

C reactive protein (CRP) levels are elevated in many diseases, including malignant tumors and cardiovascular disorders. In this study, the protein interaction network for CRP was evaluated to determine the importance of CRP and its interacting proteins in the molecular pathogenesis of hepatocellular carcinoma (HCC).

METHODS:

Isobaric tags for relative and absolute quantitation (iTRAQ) and mass spectrometry were used to identify CRP interacting proteins in SMMC7721 cells. Moreover, Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to evaluate enriched genes and pathways for differentially expressed genes using DAVID and WebGestalt. Co-immunoprecipitation and western blot analyses were employed to assess interactions between CRP and KRT8, ANXA2, ENO2, and HSP90B1.

RESULTS:

In total, 52 proteins that interact with CRP were identified. A GO analysis suggested that most of the interacting proteins were involved in CRP complexes and regulated metabolic processes. A KEGG pathway analysis suggested that most CRP-interacting proteins contribute to the TRAIL signaling pathway, Class I PI3K/Akt signaling pathway, plasma membrane estrogen receptor signaling, Nectin adhesion pathway, and S1P1 pathway. Immunoprecipitation and western blot analyses revealed interactions between CRP and KRT8, ANXA2, ENO2, and HSP90B1.

CONCLUSIONS:

iTRAQ based proteomic profiling revealed the network of CRP interacting proteins. This network may activate the PI3K/Akt signaling pathway, thereby contributing to the pathogenesis of HCC.

• Authors: Sha She, Lingyu Jiang, Zhenfang Zhang, Min Yang, Huaidong Hu, Peng Hu, Yong Liao, Yixuan Yang, Hong Ren
• Journal: Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology (Cell Physiol Biochem) Vol. 48 Issue 2 Pg. 741-752 ( 2018) ISSN: 1421-9778 [Electronic] Germany
• PMID: 30025407 (Publication Type: Journal Article)
• Copyright: © 2018 The Author(s). Published by S. Karger AG, Basel.

Chemical References

• ANXA2 protein, human
• Annexin A2
• KRT8 protein, human
• Keratin-8
• Membrane Glycoproteins
• Nectins
• RNA, Small Interfering
• TNF-Related Apoptosis-Inducing Ligand
• endoplasmin
• C-Reactive Protein
• Phosphatidylinositol 3-Kinases
• Proto-Oncogene Proteins c-akt

Topics

• Annexin A2 (metabolism)
• C-Reactive Protein (antagonists & inhibitors, genetics, metabolism)
• Carcinoma, Hepatocellular (metabolism, pathology)
• Gene Expression Profiling
• Humans
• Keratin-8 (metabolism)
• Liver Neoplasms (metabolism, pathology)
• Membrane Glycoproteins (antagonists & inhibitors, genetics, metabolism)
• Nectins (metabolism)
• Phosphatidylinositol 3-Kinases (metabolism)
• Protein Interaction Maps
• Proteomics
• Proto-Oncogene Proteins c-akt (metabolism)
• RNA Interference
• RNA, Small Interfering (metabolism)
• Signal Transduction
• TNF-Related Apoptosis-Inducing Ligand (metabolism)