Expression profiling and intracellular localization studies of the novel Proline-, Histidine-, and Glycine-rich protein 1 suggest an essential role in gastro-intestinal epithelium and a potential clinical application in colorectal cancer diagnostics.

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  • Additional Information
    • Source:
      Publisher: BioMed Central Country of Publication: England NLM ID: 100968547 Publication Model: Electronic Cited Medium: Internet ISSN: 1471-230X (Electronic) Linking ISSN: 1471230X NLM ISO Abbreviation: BMC Gastroenterol Subsets: MEDLINE
    • Publication Information:
      Original Publication: London : BioMed Central, [2001-
    • Subject Terms:
      Colorectal Neoplasms/*diagnosis ; Intestinal Mucosa/*metabolism ; Proteins/*metabolism; Blotting, Northern ; Blotting, Western ; Cell Differentiation ; Cell Line, Tumor ; Colorectal Neoplasms/pathology ; Down-Regulation ; Enterocytes/cytology ; Enterocytes/metabolism ; Glycosylation ; Humans ; Immunohistochemistry ; Intestinal Mucosa/cytology ; Lymphatic Metastasis ; Proteins/genetics ; RNA, Messenger/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Sequence Analysis, Protein
    • Abstract:
      Background: The primary function of the intestines is the absorption of water and nutrients. Although our knowledge about these processes on the cellular level is extensive, a number of important intracellular elements remain unknown. Here, we characterize the novel proline-, histidine-, glycine-rich 1 (PHGR1) mRNA and protein on the molecular level and propose a functional role of the PHGR1 protein in the intestinal and gastric epithelium.
      Methods: PHGR1 mRNA and protein expression in human tissues and cell lines were characterized by quantitative RT-PCR, in situ hybridization, Northern blotting, Western blotting, and immunohistochemistry. Glycosylation was assessed by a chemical deglycosylation assay, whereas intracellular localization was studied by immunofluorescent staining of cell line cells. PHGR1 mRNA levels in HT29 cells was reduced by RNA interference and the resulting global changes in gene expression assessed by microarray hybridization.
      Results: PHGR1 mRNA and protein were found to be expressed specifically in epithelial cells of intestinal mucosa, with the highest expression in the most mature and differentiated cells. PHGR1 protein was found to be glycosylated and to localize to both the cytoplasm and nucleus. Transcript profiling and gene ontology analysis of HT29 cells subjected to PHGR1 knockdown suggested a functional relationship with transport and metabolic processes. Examination of PHGR1 mRNA and protein levels in lymph nodes with known colorectal cancer metastases indicated that they may serve as biomarkers for detection of such metastases.
      Conclusions: Functional analyses of the novel PHGR1 mRNA and protein suggest an essential role in gastrointestinal epithelium and a clinical application in detection of colorectal cancer lymph node metastases.
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    • Grant Information:
      422102 Folke Hermansen fund
    • Contributed Indexing:
      Keywords: Cancer; Colon; Glycoprotein; Metastasis; Mucosa; Transport
    • Accession Number:
      0 (PHGR1 protein, human)
      0 (Proteins)
      0 (RNA, Messenger)
    • Publication Date:
      Date Created: 20180209 Date Completed: 20180806 Latest Revision: 20181113
    • Publication Date:
      20240104
    • Accession Number:
      PMC5803922
    • Accession Number:
      10.1186/s12876-018-0752-8
    • Accession Number:
      29415677