Glutamate receptor, ionotropic, N‑methyl D‑aspartate‑associated protein 1 promotes colorectal cancer cell proliferation and metastasis, and is negatively regulated by miR‑296‑3p

Mol Med Rep. 2021 Oct;24(4):700. doi: 10.3892/mmr.2021.12339. Epub 2021 Aug 9.

Abstract

N‑methyl D‑aspartate receptors (NMDARs) are closely associated with the development, growth and metastasis of cancer. Glutamate receptor, ionotropic, N‑methyl D‑aspartate‑associated protein 1 (GRINA) is a member of the of the NMDAR family, and its aberrant expression is associated with gastric cancer. However, the role of GRINA in colorectal cancer (CRC) is not completely understood. In the present study, expression profiles of GRINA in several CRC databases were obtained and further verified using clinical CRC samples. The effects of GRINA overexpression on CRC progression both in vivo and in vitro were assessed. Briefly, cell proliferation was detected using MTT assay, and cell migration and invasion ability were evaluated by wound healing and Transwell assay. In addition, the molecular mechanism underlying the upregulated expression of GRINA in CRC was investigated. The regulatory association between GRINA and miR‑296‑3p was detected by luciferase assay, reverse transcription‑quantitative PCR and western blotting. The results demonstrated that GRINA expression levels were significantly increased in tumor samples compared with those in healthy samples, and upregulated expression of GRINA was associated with a less favorable prognostic outcome in patients with CRC. GRINA overexpression significantly increased CRC cell proliferation, invasion and migration. Additionally, it was determined that GRINA was post‑transcriptionally regulated by microRNA (miR)‑296‑3p. Together, the results of the present study suggested the potential importance of the miR‑296‑3p/GRINA axis and highlighted potential novel targets for the management of CRC.

Keywords: N‑methyl D‑aspartate‑associated protein 1; apoptosis; colorectal cancer; glutamate receptor; invasion; ionotropic; microRNA‑296‑3p; migration.

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / pathology
  • D-Aspartic Acid / genetics
  • D-Aspartic Acid / metabolism*
  • Female
  • Gene Expression Regulation, Neoplastic
  • HEK293 Cells
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Prognosis
  • Receptors, Glutamate / metabolism*
  • Receptors, Ionotropic Glutamate / genetics
  • Receptors, Ionotropic Glutamate / metabolism*
  • Receptors, N-Methyl-D-Aspartate / genetics
  • Receptors, N-Methyl-D-Aspartate / metabolism*
  • Stomach Neoplasms / genetics
  • Xenograft Model Antitumor Assays

Substances

  • MIRN296 microRNA, human
  • MicroRNAs
  • NMDA receptor A1
  • Receptors, Glutamate
  • Receptors, Ionotropic Glutamate
  • Receptors, N-Methyl-D-Aspartate
  • D-Aspartic Acid

Grants and funding

The present work was supported by the Sichuan Youth Science and Technology Foundation (grant no. 2017JQ0039), the Scientific and Technological Cooperation Project of Nanchong City (grant no. 18SXHZ0577), the Key Scientific Project of The Affiliated Hospital of North Sichuan Medical College (grant no. 19ZD004) and the Key Scientific Project of Sichuan health and Health Committee (grant no. 19ZD005).