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

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.

SNHG25 promotes colorectal cancer metastasis by regulating MMP2

“…MiR-296-3p has been demonstrated to play a tumor suppressor role in a variety of tumors [23][24][25]. In CRC, miR-296-3p was found to inhibit tumor cell proliferation by suppressing GRINA expression [26]. Besides, Li et al found that miR-296-3p weakened cancer stem cell-like properties through targeting TGIF1 and regulated by HDAC3, which formed a feedback loop in CRC [27].…”

Membrane Stretch Gates NMDA Receptors

“…However, the levels of mechano-activation we observed with gentle membrane stretch can have a significant impact on signal transduction by neuronal extrasynaptic NMDA receptors, or those expressed in glial cells. Additionally, NMDA receptors, of unknown function, have been identified at non-traditional sites such gastrointestinal, lung, and adrenal tissue during human development (Szabo et al, 2015); and adult sites such as kidney (Leung et al, 2002), bone (Itzstein et al, 2001), myocytes (Dong et al, 2021;Seeber et al, 2004), colon (Del Valle-Pinero et al, 2007 and others, such as cancerous tissue (Yan et al, 2021).…”

Unraveling Autocrine Signaling Pathways through Metabolic Fingerprinting in Serous Ovarian Cancer Cells

“…A highly significant observation is that a subset of cells showed higher levels of Glutamate, GABA, or 5-HT ( Figure 6 ). GABA, Glu, and 5-HT have been well characterized as neurotransmitters as well as neurotrophic factors that activate intracellular signaling pathway via the stimulation of specific sets of cell surface receptors [ 23 , 24 , 25 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 ]. Evidence is emerging that they can elicit diverse non-neuronal response by stimulating their receptors in non-neuronal tissues and recent studies have shown that the extra-neuronal synthesis and release of neurotransmitters cells into the TME by the cancer cells promote tumorigenesis and tumor progression in many cancers [ 23 ].…”

“…Evidence is emerging that they can elicit diverse non-neuronal response by stimulating their receptors in non-neuronal tissues and recent studies have shown that the extra-neuronal synthesis and release of neurotransmitters cells into the TME by the cancer cells promote tumorigenesis and tumor progression in many cancers [ 23 ]. While these transmitters have been shown to stimulate cell proliferation in different cancers [ 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 ], identification of them as potential oncometabolites or their role as mediators of autocrine signaling in ovarian cancer is hitherto unreported. Our results, presented here indicate that the antagonists of these metabolism-derived ligands can effectively disrupt the autocrine signaling loop and inhibit ovarian cancer cell proliferation ( Figure 7 , Figure 8 , Figure 9 , Figure 10 and Figure 11 ).…”