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Article

Knockdown of GluA2 induces apoptosis in non-small-cell lung cancer A549 cells through the p53 signaling pathway

  • Authors:
    • Hong‑Yan Zhang
    • Wei Yang
    • Ji‑Bin Lu
  • View Affiliations / Copyright

    Affiliations: Department of Thoracic Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning 150000, P.R. China
  • Pages: 1005-1010
    |
    Published online on: May 24, 2017
       https://doi.org/10.3892/ol.2017.6234
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Abstract

α-amino-3‑hydroxy-5‑methyl-4-isoxazolepropionic acid (AMPA) receptors are important glutamatergic receptors that mediate fast excitatory synaptic transmission in the brain. Previous studies have demonstrated that glutamate ionotropic receptor AMPA type subunit 2 (GluA2), one of the four subunits that comprise AMPA receptors, is a potential novel marker for poor prognosis in patients with human lung cancer. However, the mechanisms of GluA2‑induced apoptosis, proliferation and migration in lung cancer remain unknown. The present study aimed to explore the mechanisms underlying these effects of GluA2 in human lung cancer by silencing GluA2 in A549 cells. Using the Cell Counting Kit‑8 assay, western blot analysis and acridine orange/ethidium bromide staining, downregulation of GluA2 was revealed to significantly inhibit the proliferation and significantly promote the apoptosis of A549 cells. Knockdown of GluA2 was also revealed to be associated with increased caspase‑3 activity, increased Bcl‑2‑associated X protein and Bcl-2-associated death promoter (Bad) expression, and decreased expression of B‑cell lymphoma‑2, p‑Bad and X‑linked inhibitor of apoptosis protein. In addition, GluA2 silencing upregulated cellular tumor antigen p53 (p53)/p21Cip1/Waf1/p16INK4a protein. In conclusion, these results indicate that the effects of GluA2 in lung cancer are mediated by the caspase‑3 and p53/p21Cip1/Waf1/p16INK4a signaling pathways. Therefore, GluA2 may be a potential novel therapeutic target for the treatment of lung cancer.
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1 

Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D and Bray F: Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 136:E359–E386. 2015. View Article : Google Scholar : PubMed/NCBI

2 

Sullivan I and Planchard D: ALK inhibitors in non-small cell lung cancer: The latest evidence and developments. Ther Adv Med Oncol. 8:32–47. 2016.PubMed/NCBI

3 

Ettinger DS, Akerley W, Bepler G, Blum MG, Chang A, Cheney RT, Chirieac LR, D'Amico TA, Demmy TL, Ganti AK, et al: Non-small cell lung cancer. J Natl Compr Canc Netw. 8:740–801. 2010. View Article : Google Scholar : PubMed/NCBI

4 

Larsen JE, Cascone T, Gerber DE, Heymach JV and Minna JD: Targeted therapies for lung cancer: Clinical experience and novel agents. Cancer J. 17:512–527. 2011. View Article : Google Scholar : PubMed/NCBI

5 

Reck M, Popat S, Reinmuth N, De Ruysscher D, Kerr KM and Peters S; ESMO Guidelines Working Group, : Metastatic non-small-cell lung cancer (NSCLC): ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 25 Suppl 3:iii27–iii39. 2014. View Article : Google Scholar : PubMed/NCBI

6 

Bordi P, Del Re M, Danesi R and Tiseo M: Circulating DNA in diagnosis and monitoring EGFR gene mutations in advanced non-small cell lung cancer. Transl Lung Cancer Res. 4:584–597. 2015.PubMed/NCBI

7 

Hall RD, Le TM, Haggstrom DE and Gentzler RD: Angiogenesis inhibition as a therapeutic strategy in non-small cell lung cancer (NSCLC). Transl Lung Cancer Res. 4:515–523. 2015.PubMed/NCBI

8 

Priya A, Johar K, Nair B and Wong-Riley MT: Nuclear respiratory factor 2 regulates the transcription of AMPA receptor subunit GluA2 (Gria2). Biochim Biophys Acta. 1843:3018–3028. 2014. View Article : Google Scholar : PubMed/NCBI

9 

Isaac JT, Ashby MC and McBain CJ: The role of the GluR2 subunit in AMPA receptor function and synaptic plasticity. Neuron. 54:859–871. 2007. View Article : Google Scholar : PubMed/NCBI

10 

Stepulak A, Luksch H, Gebhardt C, Uckermann O, Marzahn J, Sifringer M, Rzeski W, Staufner C, Brocke KS, Turski L and Ikonomidou C: Expression of glutamate receptor subunits in human cancers. Histochem Cell Biol. 132:435–445. 2009. View Article : Google Scholar : PubMed/NCBI

11 

Nedergaard M, Takano T and Hansen AJ: Beyond the role of glutamate as a neurotransmitter. Nat Rev Neurosci. 3:748–755. 2002. View Article : Google Scholar : PubMed/NCBI

12 

Hu H, Takano N, Xiang L, Gilkes DM, Luo W and Semenza GL: Hypoxia-inducible factors enhance glutamate signaling in cancer cells. Oncotarget. 5:8853–8868. 2014. View Article : Google Scholar : PubMed/NCBI

13 

de Groot JF, Piao Y, Lu L, Fuller GN and Yung WK: Knockdown of GluR1 expression by RNA interference inhibits glioma proliferation. J Neurooncol. 88:121–133. 2008. View Article : Google Scholar : PubMed/NCBI

14 

Choi CH, Choi JJ, Park YA, Lee YY, Song SY, Sung CO, Song T, Kim MK, Kim TJ, Lee JW, et al: Identification of differentially expressed genes according to chemosensitivity in advanced ovarian serous adenocarcinomas: Expression of GRIA2 predicts better survival. Br J Cancer. 107:91–99. 2012. View Article : Google Scholar : PubMed/NCBI

15 

Herner A, Sauliunaite D, Michalski CW, Erkan M, De Oliveira T, Abiatari I, Kong B, Esposito I, Friess H and Kleeff J: Glutamate increases pancreatic cancer cell invasion and migration via AMPA receptor activation and Kras-MAPK signaling. Int J Cancer. 129:2349–2359. 2011. View Article : Google Scholar : PubMed/NCBI

16 

Mcgahon AJ, Martin SJ, Bissonnette RP, Mahboubi A, Shi Y, Mogil RJ, Nishioka WK and Green DR: The end of the (Cell) line: Methods for the study of apoptosis in vitro. Method Cell Biol. 46:153–185. 1995. View Article : Google Scholar

17 

Ni B, Bai FF, Wei Y, Liu MJ, Feng ZX, Xiong QY, Hua LZ and Shao GQ: Apoptosis induced by lipid-associated membrane proteins from Mycoplasma hyopneumoniae in a porcine lung epithelial cell line with the involvement of caspase 3 and the MAPK pathway. Genet Mol Res. 14:11429–11443. 2015. View Article : Google Scholar : PubMed/NCBI

18 

He Y, Chen W, Hu Y, Luo B, Wu L, Qiao Y, Mo Q, Xu R, Zhou Y, Ren Z, et al: E. adenophorum induces cell cycle and apoptosis of renal cells through mitochondrial pathway and caspase activation in Saanen Goat. PLoS One. 10:e01385042015. View Article : Google Scholar : PubMed/NCBI

19 

Borges K and Dingledine R: AMPA receptors: Molecular and functional diversity. Prog Brain Res. 116:153–170. 1998. View Article : Google Scholar : PubMed/NCBI

20 

Henley JM and Wilkinson KA: AMPA receptor trafficking and the mechanisms underlying synaptic plasticity and cognitive aging. Dialogues Clin Neurosci. 15:11–27. 2013.PubMed/NCBI

21 

Serulle Y, Arancio O and Ziff EB: A role for cGMP-dependent protein kinase II in AMPA receptor trafficking and synaptic plasticity. Channels. 2:230–232. 2008. View Article : Google Scholar : PubMed/NCBI

22 

Priya A, Johar K, Nair B and Wong-Riley MT: Specificity protein 4 (Sp4) regulates the transcription of AMPA receptor subunit GluA2 (Gria2). Biochim Biophys Acta. 1843:1196–1206. 2014. View Article : Google Scholar : PubMed/NCBI

23 

Craig AM, Blackstone CD, Huganir RL and Banker G: The distribution of glutamate receptors in cultured rat hippocampal neurons: Postsynaptic clustering of AMPA-selective subunits. Neuron. 10:1055–1068. 1993. View Article : Google Scholar : PubMed/NCBI

24 

Wenthold RJ, Petralia RS, J II Blahos and Niedzielski AS: Evidence for multiple AMPA receptor complexes in hippocampal CA1/CA2 neurons. J Neurosci. 16:1982–1989. 1996.PubMed/NCBI

25 

Sommer B, Köhler M, Sprengel R and Seeburg PH: RNA editing in brain controls a determinant of ion flow in glutamate-gated channels. Cell. 67:11–19. 1991. View Article : Google Scholar : PubMed/NCBI

26 

Ikonomidou C, Bosch F, Miksa M, Bittigau P, Vöckler J, Dikranian K, Tenkova TI, Stefovska V, Turski L and Olney JW: Blockade of NMDA receptors and apoptotic neurodegeneration in the developing brain. Science. 283:70–74. 1999. View Article : Google Scholar : PubMed/NCBI

27 

Joo JY, Kim BW, Lee JS, Park JY, Kim S, Yun YJ, Lee SH, Lee SH, Rhim H and Son H: Activation of NMDA receptors increases proliferation and differentiation of hippocampal neural progenitor cells. J Cell Sci. 120:1358–1370. 2007. View Article : Google Scholar : PubMed/NCBI

28 

Yoshioka A, Ikegaki N, Williams M and Pleasure D: Expression of N-methyl-D-aspartate (NMDA) and non-NMDA glutamate receptor genes in neuroblastoma, medulloblastoma and other cells lines. J Neurosci Res. 46:164–178. 1996. View Article : Google Scholar : PubMed/NCBI

29 

Takeda M, Haga M, Yamada H, Kinoshita M, Otsuka M, Tsuboi S and Moriyama Y: Ionotropic glutamate receptors expressed in human retinoblastoma Y79 cells. Neurosci Lett. 294:97–100. 2000. View Article : Google Scholar : PubMed/NCBI

30 

Rzeski W, Ikonomidou C and Turski L: Glutamate antagonists limit tumor growth. Biochem Pharmacol. 64:1195–1200. 2002. View Article : Google Scholar : PubMed/NCBI

31 

Ishiuchi S, Yoshida Y, Sugawara K, Aihara M, Ohtani T, Watanabe T, Saito N, Tsuzuki K, Okado H, Miwa A, et al: Ca2+-permeable AMPA receptors regulate growth of human glioblastoma via Akt activation. J Neurosci. 27:7987–8001. 2007. View Article : Google Scholar : PubMed/NCBI

32 

Lin HI, Lee YJ, Chen BF, Tsai MC, Lu JL, Chou CJ and Jow GM: Involvement of Bcl-2 family, cytochrome c and caspase 3 in induction of apoptosis by beauvericin in human non-small cell lung cancer cells. Cancer Lett. 230:248–259. 2005. View Article : Google Scholar : PubMed/NCBI

33 

Paulsen M, Ussat S, Jakob M, Scherer G, Lepenies I, Schütze S, Kabelitz D and Adam-Klages S: Interaction with XIAP prevents full caspase-3/−7 activation in proliferating human T lymphocytes. Eur J Immunol. 38:1979–1987. 2008. View Article : Google Scholar : PubMed/NCBI

34 

Feng J, Zhang S, Wu K, Wang B, Wong JY, Jiang H, Xu R, Ying L, Huang H, Zheng X, et al: Combined effects of suberoylanilide hydroxamic acid and cisplatin on radiation sensitivity and cancer cell invasion in non-small-cell lung cancer. Mol Cancer Ther. 15:842–853. 2016. View Article : Google Scholar : PubMed/NCBI

35 

Rajagopalan P, Alahmari KA, Elbessoumy AA, Balasubramaniam M, Suresh R, Shariff ME and Chandramoorthy HC: Biological evaluation of 2-arylidene-4, 7-dimethyl indan-1-one (FXY-1): A novel Akt inhibitor with potent activity in lung cancer. Cancer Chemother Pharmacol. 77:393–404. 2016. View Article : Google Scholar : PubMed/NCBI

36 

Smardova J, Liskova K, Ravcukova B, Malcikova J, Hausnerova J, Svitakova M, Hrabalkova R, Zlamalikova L, Stano-Kozubik K, Blahakova I, et al: Complex analysis of the p53 tumor suppressor in lung carcinoma. Oncol Rep. 35:1859–1867. 2016.PubMed/NCBI

37 

Zhang G, An Y, Lu X, Zhong H, Zhu Y, Wu Y, Ma F, Yang J, Liu Y, Zhou Z, et al: A Novel naphthalimide compound restores p53 function in non-small-cell lung cancer by reorganizing the bak-Bcl-xl complex and triggering transcriptional regulation. J Biol Chem. 291:4211–4225. 2016. View Article : Google Scholar : PubMed/NCBI

38 

Iwamoto FM, Kreisl TN, Kim L, Duic JP, Butman JA, Albert PS and Fine HA: Phase 2 trial of talampanel, a glutamate receptor inhibitor, for adults with recurrent malignant gliomas. Cancer. 116:1776–1782. 2010. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Zhang HY, Yang W and Lu JB: Knockdown of GluA2 induces apoptosis in non-small-cell lung cancer A549 cells through the p53 signaling pathway. Oncol Lett 14: 1005-1010, 2017.
APA
Zhang, H., Yang, W., & Lu, J. (2017). Knockdown of GluA2 induces apoptosis in non-small-cell lung cancer A549 cells through the p53 signaling pathway. Oncology Letters, 14, 1005-1010. https://doi.org/10.3892/ol.2017.6234
MLA
Zhang, H., Yang, W., Lu, J."Knockdown of GluA2 induces apoptosis in non-small-cell lung cancer A549 cells through the p53 signaling pathway". Oncology Letters 14.1 (2017): 1005-1010.
Chicago
Zhang, H., Yang, W., Lu, J."Knockdown of GluA2 induces apoptosis in non-small-cell lung cancer A549 cells through the p53 signaling pathway". Oncology Letters 14, no. 1 (2017): 1005-1010. https://doi.org/10.3892/ol.2017.6234
Copy and paste a formatted citation
x
Spandidos Publications style
Zhang HY, Yang W and Lu JB: Knockdown of GluA2 induces apoptosis in non-small-cell lung cancer A549 cells through the p53 signaling pathway. Oncol Lett 14: 1005-1010, 2017.
APA
Zhang, H., Yang, W., & Lu, J. (2017). Knockdown of GluA2 induces apoptosis in non-small-cell lung cancer A549 cells through the p53 signaling pathway. Oncology Letters, 14, 1005-1010. https://doi.org/10.3892/ol.2017.6234
MLA
Zhang, H., Yang, W., Lu, J."Knockdown of GluA2 induces apoptosis in non-small-cell lung cancer A549 cells through the p53 signaling pathway". Oncology Letters 14.1 (2017): 1005-1010.
Chicago
Zhang, H., Yang, W., Lu, J."Knockdown of GluA2 induces apoptosis in non-small-cell lung cancer A549 cells through the p53 signaling pathway". Oncology Letters 14, no. 1 (2017): 1005-1010. https://doi.org/10.3892/ol.2017.6234
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