Glutamate receptor ionotropic, kainate 1 serves as a novel tumor suppressor of colorectal carcinoma and predicts clinical prognosis

Abstract

Colorectal cancer (CRC) is one of the most malignant cancers worldwide. However, the mechanisms of initiation and development of CRC are still largely unclear. The present study aimed to investigate the biological function and prognosis of glutamate receptor ionotropic, kainate 1 (GRIK1) in CRC. GRIK1 expression levels were analyzed in tissue microarrays containing 80 primary CRC samples using immunohistochemistry (IHC). The association between GRIK1 expression levels, clinicopathological factors and the prognosis was also investigated using Spearman's correlation analysis and Kaplan-Meier analysis, respectively. After genetic knockdown or overexpression of GRIK1, invasion/migration assays, proliferation assay, soft agar/colony formation assays, western blotting, reverse transcription-quantitative PCR and tumor xenograft models were used to investigate the function of GRIK1 both in vitro in two CRC cell lines, HCT116 and SW620, and in vivo. The results revealed that the expression levels of GRIK1 were significantly downregulated in CRC samples. Furthermore, IHC analysis indicated that the downregulated expression levels of GRIK1 were significantly associated with lymph node status and tumor size. In addition, patients with CRC with low GRIK1 expression levels demonstrated a consistently poor overall survival. The overexpression of GRIK1 inhibited the proliferation, colony formation, migration, invasion and epithelial-mesenchymal transition of HCT116 cells in vitro. In contrast, the genetic knockdown of GRIK1 promoted the proliferative, colony forming, migratory and invasive abilities of SW620 cells in vitro. Moreover, the overexpression of GRIK1 inhibited tumor growth, and liver and lung metastasis of CRC in vivo. In conclusion, the findings of the present study suggested that GRIK1 may serve as a tumor suppressor in CRC, and upregulated expression levels of GRIK1 may predict an improved prognosis for patients with CRC.

GRIK1 promotes glioblastoma malignancy and is a novel prognostic factor of poor prognosis

“…In brain regions responsible for learning and memory, GRIK1 is encoded by the GRIK1 gene [17], which is located on chromosome 21q21.1-22.1 [16]. In previous studies, the relationship between GRIK1 and disease has been studied in multiple fields [22,23,[27][28][29]31]. However, GRIK1's pathogenic roles and mechanisms in GBM are still unknown.…”

“…The GRIK1 gene is known to be particularly implicated in schizophrenia within the glutamate system [ 21 ]. In addition, several recent reports have suggested that GRIK1 may be an important factor for predicting the progression or prognosis of colorectal carcinoma [ 22 ], and breast tumor [ 23 ], it is the most prevalent kinds of cancer in women and one of the main causes of cancer deaths [ 24 ], and the progression of breast cancer is also related to many elements, such as metastasis-related gene signature [ 25 ], and has_circ_0000069 [ 26 ]. A polymorphism (rs2832407) in GRIK1, which encodes the GluK1 kainate subunit, modifies topiramate-related reduction in heavy drinking [ 27 , 28 ], while a GRIKI polymorphism forecasts negative effects after topiramate therapy [ 28 ].…”

Influence of acidic metabolic environment on differentiation of stem cell-derived cardiomyocytes

“…Lin28 is associated with stem cell metabolism and pluripotency ( 10 ) and regulates the activation of early cardiomyocytes ( 42 ), while TCIM is associated with a poor differentiation state of cells ( 43 ). Grik1 is thought to restrain cell proliferation ( 44 ), while Dgkk is associated with cardiomyocyte hypertrophy ( 45 ). These results further support a role for lactate in stimulating cardiomyocyte proliferation at the gene expression level.…”