Identification of candidate biomarkers associated with apoptosis in melanosis coli: GNG5, LPAR3, MAPK8, and PSMC6

Biosci Rep. 2019 Jan 18;39(1):BSR20181369. doi: 10.1042/BSR20181369. Print 2019 Jan 31.

Abstract

Purpose: Melanosis coli (MC) is a disorder of pigmentation of the wall of the colon, often identified at the time of colonoscopy. The aim of the present study is to identify candidate biomarkers for MC. Methods: The transcriptome data for MC (GSE78933) with five MC tissues and five corresponding normal tissues is obtained from the NCBI Gene Expression Omnibus (GEO) database. R/Bioconductor package limma was used to screen differently expressed genes (DEGs). ClueGO of cytoscape was applied for Gene Ontology (GO) functional and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Based on STRING V10 database, protein-protein interaction (PPI) network was constructed. The pathological tissue and normal tissue from 23 MC patients and 23 controls were collected, respectively. The relative expression of hub nodes was detected by qRT-PCR and Western blot. For regulating the expression of these genes, overexpression vector was constructed or siRNA transfection was used. Finally, apoptosis was detected by flow cytometry. Results: Total 1342 DEGs were screened, including 786 up-regulated and 556 down-regulated genes. These genes were mainly enriched in stimulatory C-type lectin receptor signaling pathway, polysaccharide biosynthetic process, intracellular, and oxidative phosphorylation. PPI network was then constructed with 426 DEGs and 895 interactions. Thereinto, G-protein subunit γ 5 (GNG5), lysophosphatidic acid receptor 3 (LPAR3), mitogen-activated protein kinase 8 (MAPK8), NHP2L1, proteasome 26S subunit, ATPase 6 (PSMC6), and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit β (PIK3CB) were hub nodes with higher degree. RT-PCR and Western blot results showed that GNG5, LPAR3, MAPK8, and PSMC6 were differently expressed with significance. The expression of these screened genes is also related with cell apoptosis. Conclusion: GNG5, LPAR3, MAPK8, and PSMC6 might be candidate biomarkers associated with apoptosis in MC.

Keywords: Melanosis coli; biomarkers; cell apoptosis; differently express; protein-protein interaction network.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATPases Associated with Diverse Cellular Activities / genetics*
  • ATPases Associated with Diverse Cellular Activities / metabolism
  • Apoptosis / physiology
  • Biomarkers
  • Case-Control Studies
  • Colonic Diseases / genetics*
  • GTP-Binding Protein gamma Subunits / genetics*
  • GTP-Binding Protein gamma Subunits / metabolism
  • Humans
  • Melanosis / genetics*
  • Mitogen-Activated Protein Kinase 8 / genetics*
  • Mitogen-Activated Protein Kinase 8 / metabolism
  • Proteasome Endopeptidase Complex / genetics*
  • Proteasome Endopeptidase Complex / metabolism
  • Protein Interaction Maps
  • Receptors, Lysophosphatidic Acid / genetics*
  • Receptors, Lysophosphatidic Acid / metabolism
  • Transcriptome

Substances

  • Biomarkers
  • GNG5 protein, human
  • GTP-Binding Protein gamma Subunits
  • Receptors, Lysophosphatidic Acid
  • Mitogen-Activated Protein Kinase 8
  • Proteasome Endopeptidase Complex
  • ATPases Associated with Diverse Cellular Activities
  • PSMC6 protein, human