HIP1R acts as a tumor suppressor in gastric cancer by promoting cancer cell apoptosis and inhibiting migration and invasion through modulating Akt

J Clin Lab Anal. 2020 Sep;34(9):e23425. doi: 10.1002/jcla.23425. Epub 2020 Jun 16.

Abstract

Background: Huntingtin-interacting protein 1-related (HIP1R) is a multi-domain gene that exerts many cellular functions including altering T cell-mediated cytotoxicity and controlling intracellular trafficking. However, its clinical significance and function in gastric cancer (GC) have not been described.

Methods: The expression levels of HIP1R were tested by the transcriptional and translational expression analysis and immunohistochemistry (IHC) in matched adjacent non-tumorous vs tumor tissue specimens. The biological function of HIP1R on apoptosis, migration, and proliferation was evaluated by flow cytometry, Transwell, Cell Counting Kit-8 (CCK-8) assays, colony formation assays, and EdU labeling assays, respectively.

Results: We found downregulated HIP1R in GC compared with adjacent non-tumorous tissue, and HIP1R expression associated with N classification. We further found that the expression of HIP1R could induce apoptosis and inhibit proliferation, migration, invasion of GC cells, possibly through modulating Akt.

Conclusions: Our data indicate that HIP1R may act as a potential diagnostic biomarker and a tumor suppressor gene in GC, potentially representing a novel therapeutic target for future GC treatment.

Keywords: apoptosis; gastric cancer; huntingtin-interacting protein 1-related; invasion; migration.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Apoptosis*
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Cell Movement*
  • Cell Proliferation
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Male
  • Microfilament Proteins / genetics
  • Microfilament Proteins / metabolism*
  • Middle Aged
  • Neoplasm Invasiveness
  • Prognosis
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology*
  • Survival Rate
  • Tumor Cells, Cultured

Substances

  • Adaptor Proteins, Signal Transducing
  • Biomarkers, Tumor
  • HIP1R protein, human
  • Microfilament Proteins
  • Proto-Oncogene Proteins c-akt