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Article

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

  • Authors:
    • Zhong Ren
    • Jingzheng Liu
    • Liqing Yao
    • Jian Li
    • Zhipeng Qi
    • Bing Li
  • View Affiliations / Copyright

    Affiliations: Endoscopy Research Institute, Endoscopy Center, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China
  • Article Number: 167
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    Published online on: October 9, 2020
       https://doi.org/10.3892/etm.2020.9296
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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.
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1 

Rawla P, Sunkara T and Barsouk A: Epidemiology of colorectal cancer: Incidence, mortality, survival, and risk factors. Prz Gastroenterol. 14:89–103. 2019.PubMed/NCBI View Article : Google Scholar

2 

Winawer S, Fletcher R, Rex D, Bond J, Burt R, Ferrucci J, Ganiats T, Levin T, Woolf S, Johnson D, et al: Gastrointestinal Consortium Panel: Colorectal cancer screening and surveillance: Clinical guidelines and rationale-Update based on new evidence. Gastroenterology. 124:544–560. 2003.PubMed/NCBI View Article : Google Scholar

3 

Rees M, Tekkis PP, Welsh FK, O'Rourke T and John TG: Evaluation of long-term survival after hepatic resection for metastatic colorectal cancer: A multifactorial model of 929 patients. Ann Surg. 247:125–135. 2008.PubMed/NCBI View Article : Google Scholar

4 

Wei Y, Zhang X, Wang G, Zhou Y, Luo M, Wang S and Hong C: The impacts of pretreatment circulating eosinophils and basophils on prognosis of stage Ⅰ-Ⅲ colorectal cancer. Asia Pac J Clin Oncol. 14:e243–e251. 2018.PubMed/NCBI View Article : Google Scholar

5 

Shi W, Ye Z, Zhuang L, Li Y, Shuai W, Zuo Z, Mao X, Liu R, Wu J, Chen S, et al: Olfactomedin 1 negatively regulates NF-κB signalling and suppresses the growth and metastasis of colorectal cancer cells. J Pathol. 240:352–365. 2016.PubMed/NCBI View Article : Google Scholar

6 

Qiu YY, Hu Q, Tang QF, Feng W, Hu SJ, Liang B, Peng W and Yin PH: MicroRNA-497 and bufalin act synergistically to inhibit colorectal cancer metastasis. Tumour Biol. 35:2599–2606. 2014.PubMed/NCBI View Article : Google Scholar

7 

Yang Y, Weng W, Peng J, Hong L, Yang L, Toiyama Y, Gao R, Liu M, Yin M, Pan C, et al: Fusobacterium nucleatum increases proliferation of colorectal cancer cells and tumor development in mice by activating toll-like receptor 4 signaling to nuclear factor-κB, and up-regulating expression of microRNA-21. Gastroenterology. 152:851–866.e24. 2017.PubMed/NCBI View Article : Google Scholar

8 

Carethers JM and Jung BH: Genetics and genetic biomarkers in sporadic colorectal cancer. Gastroenterology. 149:1177–1190.e3. 2015.PubMed/NCBI View Article : Google Scholar

9 

Okugawa Y, Grady WM and Goel A: Epigenetic alterations in colorectal cancer: Emerging biomarkers. Gastroenterology. 149:1204–1225.e12. 2015.PubMed/NCBI View Article : Google Scholar

10 

Prahallad A, Sun C, Huang S, Di Nicolantonio F, Salazar R, Zecchin D, Beijersbergen RL, Bardelli A and Bernards R: Unresponsiveness of colon cancer to BRAF(V600E) inhibition through feedback activation of EGFR. Nature. 483:100–103. 2012.PubMed/NCBI View Article : Google Scholar

11 

Barras D, Missiaglia E, Wirapati P, Sieber OM, Jorissen RN, Love C, Molloy PL, Jones IT, McLaughlin S, Gibbs P, et al: BRAF V600E mutant colorectal cancer subtypes based on gene expression. Clin Cancer Res. 23:104–115. 2017.PubMed/NCBI View Article : Google Scholar

12 

Arriba M, García JL, Inglada-Pérez L, Rueda D, Osorio I, Rodríguez Y, Álvaro E, Sánchez R, Fernández T, Pérez J, et al: DNA copy number profiling reveals different patterns of chromosomal instability within colorectal cancer according to the age of onset. Mol Carcinog. 55:705–716. 2016.PubMed/NCBI View Article : Google Scholar

13 

Koi M, Garcia M, Choi C, Kim HR, Koike J, Hemmi H, Nagasaka T, Okugawa Y, Toiyama Y, Kitajima T, et al: Microsatellite alterations with allelic loss at 9p24.2 signify less-aggressive colorectal cancer metastasis. Gastroenterology. 150:944–955. 2016.PubMed/NCBI View Article : Google Scholar

14 

Voorneveld PW, Kodach LL, Jacobs RJ, Liv N, Zonnevylle AC, Hoogenboom JP, Biemond I, Verspaget HW, Hommes DW, de Rooij K, et al: Loss of SMAD4 alters BMP signaling to promote colorectal cancer cell metastasis via activation of Rho and ROCK. Gastroenterology. 147:196–208.e13. 2014.PubMed/NCBI View Article : Google Scholar

15 

Dow LE, O'Rourke KP, Simon J, Tschaharganeh DF, van Es JH, Clevers H and Lowe SW: Apc restoration promotes cellular differentiation and reestablishes crypt homeostasis in colorectal cancer. Cell. 161:1539–1552. 2015.PubMed/NCBI View Article : Google Scholar

16 

Li X, Chen T, Shi Q, Li J, Cai S, Zhou P, Zhong Y and Yao L: Angiopoietin-like 4 enhances metastasis and inhibits apoptosis via inducing bone morphogenetic protein 7 in colorectal cancer cells. Biochem Biophys Res Commun. 467:128–134. 2015.PubMed/NCBI View Article : Google Scholar

17 

Yang C, Wang S, Ruan H, Li B, Cheng Z, He J, Zuo Q, Yu C, Wang H, Lv Y, et al: Downregulation of PDK4 increases lipogenesis and associates with poor prognosis in hepatocellular carcinoma. J Cancer. 10:918–926. 2019.PubMed/NCBI View Article : Google Scholar

18 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Δ Δ C(T)) method. Methods. 25:402–408. 2001.PubMed/NCBI View Article : Google Scholar

19 

Hasle H, Clemmensen IH and Mikkelsen M: Risks of leukaemia and solid tumours in individuals with Down syndrome. Lancet. 355:165–169. 2000.PubMed/NCBI View Article : Google Scholar

20 

Hasle H, Friedman JM, Olsen JH and Rasmussen SA: Low risk of solid tumors in persons with Down syndrome. Genet Med. 18:1151–1157. 2016.PubMed/NCBI View Article : Google Scholar

21 

Pussegoda KA: Down syndrome patients are less likely to develop cancer. Clin Genet. 78:35–37. 2010.PubMed/NCBI View Article : Google Scholar

22 

Jin H, Wang C, Jin G, Ruan H, Gu D, Wei L, Wang H, Wang N, Arunachalam E, Zhang Y, et al: Regulator of calcineurin 1 gene isoform 4, down-regulated in hepatocellular carcinoma, prevents proliferation, migration, and invasive activity of cancer cells and metastasis of orthotopic tumors by inhibiting nuclear translocation of NFAT1. Gastroenterology. 153:799–811.e33. 2017.PubMed/NCBI View Article : Google Scholar

23 

Dey N, Krie A, Klein J, Williams K, McMillan A, Elsey R, Sun Y, Williams C, De P and Leyland-Jones B: Down syndrome and triple negative breast cancer: A rare occurrence of distinctive clinical relationship. Int J Mol Sci. 18(E1218)2017.PubMed/NCBI View Article : Google Scholar

24 

Kuwahara K, Yamamoto-Ibusuki M, Zhang Z, Phimsen S, Gondo N, Yamashita H, Takeo T, Nakagata N, Yamashita D, Fukushima Y, et al: GANP protein encoded on human chromosome 21/mouse chromosome 10 is associated with resistance to mammary tumor development. Cancer Sci. 107:469–477. 2016.PubMed/NCBI View Article : Google Scholar

25 

Hattori M, Fujiyama A, Taylor TD, Watanabe H, Yada T, Park HS, Toyoda A, Ishii K, Totoki Y, Choi DK, et al: Chromosome 21 mapping and sequencing consortium: The DNA sequence of human chromosome 21. Nature. 405:311–319. 2000.PubMed/NCBI View Article : Google Scholar

26 

Li W, Wang X and Li S: Investigation of copy number variations on chromosome 21 detected by comparative genomic hybridization (CGH) microarray in patients with congenital anomalies. Mol Cytogenet. 11(42)2018.PubMed/NCBI View Article : Google Scholar

27 

Barbon A and Barlati S: Genomic organization, proposed alternative splicing mechanisms, and RNA editing structure of GRIK1. Cytogenet Cell Genet. 88:236–239. 2000.PubMed/NCBI View Article : Google Scholar

28 

Sander T, Hildmann T, Kretz R, Fürst R, Sailer U, Bauer G, Schmitz B, Beck-Mannagetta G, Wienker TF and Janz D: Allelic association of juvenile absence epilepsy with a GluR5 kainate receptor gene (GRIK1) polymorphism. Am J Med Genet. 74:416–421. 1997.PubMed/NCBI

29 

Matsuda K: Novel susceptibility loci for hepatocellular carcinoma in chronic HBV carriers. Hepatobiliary Surg Nutr. 1:59–60. 2012.PubMed/NCBI View Article : Google Scholar

30 

Luo Y, Xie C, Brocker CN, Fan J, Wu X, Feng L, Wang Q, Zhao J, Lu D, Tandon M, et al: Intestinal PPARα protects against colon carcinogenesis via regulation of methyltransferases DNMT1 and PRMT6. Gastroenterology. 157:744–759.e4. 2019.PubMed/NCBI View Article : Google Scholar

31 

Minbay Z, Serter Kocoglu S, Gok Yurtseven D and Eyigor O: Immunohistochemical localization of ionotropic glutamate receptors in the rat red nucleus. Bosn J Basic Med Sci. 17:29–37. 2017.PubMed/NCBI View Article : Google Scholar

32 

Kuo TC, Chen CK, Hua KT, Yu P, Lee WJ, Chen MW, Jeng YM, Chien MH, Kuo KT, Hsiao M, et al: Glutaminase 2 stabilizes Dicer to repress Snail and metastasis in hepatocellular carcinoma cells. Cancer Lett. 383:282–294. 2016.PubMed/NCBI View Article : Google Scholar

33 

Cacace A, Sboarina M, Vazeille T and Sonveaux P: Glutamine activates STAT3 to control cancer cell proliferation independently of glutamine metabolism. Oncogene. 36:2074–2084. 2017.PubMed/NCBI View Article : Google Scholar

34 

Christa L, Simon MT, Flinois JP, Gebhardt R, Brechot C and Lasserre C: Overexpression of glutamine synthetase in human primary liver cancer. Gastroenterology. 106:1312–1320. 1994.PubMed/NCBI View Article : Google Scholar

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Copy and paste a formatted citation
Spandidos Publications style
Ren Z, Liu J, Yao L, Li J, Qi Z and Li B: Glutamate receptor ionotropic, kainate 1 serves as a novel tumor suppressor of colorectal carcinoma and predicts clinical prognosis. Exp Ther Med 20: 167, 2020.
APA
Ren, Z., Liu, J., Yao, L., Li, J., Qi, Z., & Li, B. (2020). Glutamate receptor ionotropic, kainate 1 serves as a novel tumor suppressor of colorectal carcinoma and predicts clinical prognosis. Experimental and Therapeutic Medicine, 20, 167. https://doi.org/10.3892/etm.2020.9296
MLA
Ren, Z., Liu, J., Yao, L., Li, J., Qi, Z., Li, B."Glutamate receptor ionotropic, kainate 1 serves as a novel tumor suppressor of colorectal carcinoma and predicts clinical prognosis". Experimental and Therapeutic Medicine 20.6 (2020): 167.
Chicago
Ren, Z., Liu, J., Yao, L., Li, J., Qi, Z., Li, B."Glutamate receptor ionotropic, kainate 1 serves as a novel tumor suppressor of colorectal carcinoma and predicts clinical prognosis". Experimental and Therapeutic Medicine 20, no. 6 (2020): 167. https://doi.org/10.3892/etm.2020.9296
Copy and paste a formatted citation
x
Spandidos Publications style
Ren Z, Liu J, Yao L, Li J, Qi Z and Li B: Glutamate receptor ionotropic, kainate 1 serves as a novel tumor suppressor of colorectal carcinoma and predicts clinical prognosis. Exp Ther Med 20: 167, 2020.
APA
Ren, Z., Liu, J., Yao, L., Li, J., Qi, Z., & Li, B. (2020). Glutamate receptor ionotropic, kainate 1 serves as a novel tumor suppressor of colorectal carcinoma and predicts clinical prognosis. Experimental and Therapeutic Medicine, 20, 167. https://doi.org/10.3892/etm.2020.9296
MLA
Ren, Z., Liu, J., Yao, L., Li, J., Qi, Z., Li, B."Glutamate receptor ionotropic, kainate 1 serves as a novel tumor suppressor of colorectal carcinoma and predicts clinical prognosis". Experimental and Therapeutic Medicine 20.6 (2020): 167.
Chicago
Ren, Z., Liu, J., Yao, L., Li, J., Qi, Z., Li, B."Glutamate receptor ionotropic, kainate 1 serves as a novel tumor suppressor of colorectal carcinoma and predicts clinical prognosis". Experimental and Therapeutic Medicine 20, no. 6 (2020): 167. https://doi.org/10.3892/etm.2020.9296
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