Specific protein 1 depletion attenuates glucose uptake and proliferation of human glioma cells by regulating GLUT3 expression

Zheng,Chuanyi; Yang,Kun; Zhang,Maoying; Zou,Mingming; Bai,Enqi; Ma,Quanhong; Xu,Ruxiang

doi:10.3892/ol.2016.4599

Specific protein 1 depletion attenuates glucose uptake and proliferation of human glioma cells by regulating GLUT3 expression

Authors:
- Chuanyi Zheng
- Kun Yang
- Maoying Zhang
- Mingming Zou
- Enqi Bai
- Quanhong Ma
- Ruxiang Xu
View Affiliations

Affiliations: Affiliated Bayi Brain Hospital, General Hospital of Beijing Military Region, Southern Medical University, Beijing 100072, P.R. China, Department of Neurosurgery, The Affiliated Hospital of Hainan Medical College, Haikou, Hainan 570102, P.R. China, Jiangsu Key Laboratory of Translational Research and Therapy for Neuro‑Psycho‑Diseases, Institute of Neuroscience, Soochow University, Suzhou, Jiangsu 215123, P.R. China
Published online on: May 17, 2016 https://doi.org/10.3892/ol.2016.4599
Pages: 125-131
Copyright: © Zheng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

It has been reported previously that the expression of glucose transporter member 3 (GLUT3) is increased in malignant glioma cells compared with normal glial cells. However, the regulating mechanism that causes this phenomenon remains unknown. The present study investigated the regulating role of transcription factor specific protein 1 (Sp1) in GLUT3 expression in a human glioma cell line. In the present study, Sp1 was identified to directly bind to the GLUT3 5'‑untranslated region in human glioma U251 cells. Small interfering RNA‑ and the Sp1-inhibitor mithramycin A-mediated Sp1 knockdown experiments revealed that Sp1 depletion decreased glucose uptake and inhibited cell growth and invasion of U251 cells by downregulating GLUT3 expression. Therefore Sp1 is an important positive regulator for the expression of GLUT3 in human glioma cells, and may explain the overexpression of GLUT3 in U251 cells. These results suggest that Sp1 may have a role in glioma treatment.

View Figures

View References

1	Ahmed R, Oborski MJ, Hwang M, Lieberman FS and Mountz JM: Malignant gliomas: Current perspectives in diagnosis, treatment and early response assessment using advanced quantitative imaging methods. Cancer Manag Res. 6:149–170. 2014.PubMed/NCBI
2	Chung WJ, Lyons SA, Nelson GM, Hamza H, Gladson CL, Gillespie GY and Sontheimer H: Inhibition of cystine uptake disrupts the growth of primary brain tumors. J Neurosci. 25:7101–7110. 2005. View Article : Google Scholar : PubMed/NCBI
3	Flavahan WA, Wu Q, Hitomi M, Rahim N, Kim Y, Sloan AE, Weil RJ, Nakano I, Sarkaria JN, Stringer BW, et al: Brain tumor initiating cells adapt to restricted nutrition through preferential glucose uptake. Nat Neurosci. 16:1373–1382. 2013. View Article : Google Scholar : PubMed/NCBI
4	Zheng J: Energy metabolism of cancer: Glycolysis versus oxidative phosphorylation (Review). Oncol Lett. 4:1151–1157. 2012.PubMed/NCBI
5	Walker-Samuel S, Ramasawmy R, Torrealdea F, Rega M, Rajkumar V, Johnson SP, Richardson S, Gonçalves M, Parkes HG, Arstad E, et al: In vivo imaging of glucose uptake and metabolism in tumors. Nat Med. 19:1067–1072. 2013. View Article : Google Scholar : PubMed/NCBI
6	Rodríguez-Enríquez S, Marin-Hernández A, Gallardo-Pérez JC and Moreno-Sánchez R: Kinetics of transport and phosphorylation of glucose in cancer cells. J Cell Physiol. 221:552–559. 2009. View Article : Google Scholar : PubMed/NCBI
7	Boado RJ, Black KL and Pardridge WM: Gene expression of GLUT3 and GLUT1 glucose transporters in human brain tumors. Brain Res Mol Brain Res. 27:51–57. 1994. View Article : Google Scholar : PubMed/NCBI
8	Nagamatsu S, Sawa H, Wakizaka A and Hoshino T: Expression of facilitative glucose transporter isoforms in human brain tumors. J Neurochem. 61:2048–2053. 1993. View Article : Google Scholar : PubMed/NCBI
9	Nishioka T, Oda Y, Seino Y, Yamamoto T, Inagaki N, Yano H, Imura H, et al: Distribution of the glucose transporters in human brain tumors. Cancer Res. 52:3972–3979. 1992.PubMed/NCBI
10	Li L and Davie JR: The role of Sp1 and Sp3 in normal and cancer cell biology. Ann Anat. 192:275–283. 2010. View Article : Google Scholar : PubMed/NCBI
11	Copland JA, Pardini AW, Wood TG, Yin D, Green A, Bodenburg YH, Urban RJ and Stuart CA: IGF-1 controls GLUT3 expression in muscle via the transcriptional factor Sp1. Biochim Biophys Acta. 1769:631–640. 2007. View Article : Google Scholar : PubMed/NCBI
12	Hsu TI, Wang MC, Chen SY, Yeh YM, Su WC, Chang WC and Hung JJ: Sp1 expression regulates lung tumor progression. Oncogene. 31:3973–3988. 2012. View Article : Google Scholar : PubMed/NCBI
13	Kou XX, Hao T, Meng Z, Zhou YH and Gan YH: Acetylated Sp1 inhibits PTEN expression through binding to PTEN core promoter and recruitment of HDAC1 and promotes cancer cell migration and invasion. Carcinogenesis. 34:58–67. 2013. View Article : Google Scholar : PubMed/NCBI
14	Safe S, Imanirad P, Sreevalsan S, Nair V and Jutooru I: Transcription factor Sp1, also known as specificity protein 1 as a therapeutic target. Expert Opin Ther Targets. 18:759–769. 2014. View Article : Google Scholar : PubMed/NCBI
15	Sleiman SF, Langley BC, Basso M, Berlin J, Xia L, Payappilly JB, Kharel MK, et al: Mithramycin is a gene-selective Sp1 inhibitor that identifies a biological intersection between cancer and neurodegeneration. J Neurosci. 31:6858–6870. 2011. View Article : Google Scholar : PubMed/NCBI
16	Malek A, Núñez LE, Magistri M, Brambilla L, Jovic S, Carbone GM, Morís F and Catapano CV: Modulation of the activity of Sp transcription factors by mithramycin analogues as a new strategy for treatment of metastatic prostate cancer. PLoS One. 7:e351302012. View Article : Google Scholar : PubMed/NCBI
17	Copland JA, Pardini AW, Wood TG, Yin D, Green A, Bodenburg YH, Urban RJ and Stuart CA: IGF-1 controls GLUT3 expression in muscle via the transcriptional factor Sp1. Biochim Biophys Acta. 1769:631–640. 2007. View Article : Google Scholar : PubMed/NCBI
18	Guan H, Cai J, Zhang N, Wu J, Yuan J, Li J and Li M: Sp1 is upregulated in human glioma, promotes MMP-2-mediated cell invasion and predicts poor clinical outcome. Int J Cancer. 130:593–601. 2012. View Article : Google Scholar : PubMed/NCBI
19	Garcia-Huerta P, Díaz-Hernandez M, Delicado EG, Pimentel-Santillana M, Miras-Portugal MT and Gómez-Villafuertes R: The specificity protein factor Sp1 mediates transcriptional regulation of P2X7 receptors in the nervous system. J Biol Chem. 287:44628–44644. 2012. View Article : Google Scholar : PubMed/NCBI
20	Maher F, Davies-Hill TM, Lysko PG, Henneberry RC and Simpson IA: Expression of two glucose transporters, GLUT1 and GLUT3, in cultured cerebellar neurons: Evidence for neuron-specific expression of GLUT3. Mol Cell Neurosci. 2:351–360. 1991. View Article : Google Scholar : PubMed/NCBI
21	Macheda ML, Rogers S and Best JD: Molecular and cellular regulation of glucose transporter (GLUT) proteins in cancer. J Cell Physiol. 202:654–662. 2005. View Article : Google Scholar : PubMed/NCBI
22	Seznec J, Silkenstedt B and Naumann U: Therapeutic effects of the Sp1 inhibitor mithramycin A in glioblastoma. J Neurooncol. 101:365–377. 2011. View Article : Google Scholar : PubMed/NCBI
23	Amann T and Hellerbrand C: GLUT1 as a therapeutic target in hepatocellular carcinoma. Expert Opin Ther Targets. 13:1411–1427l. 2009. View Article : Google Scholar : PubMed/NCBI
24	Blume SW, Snyder RC, Ray R, Thomas S, Koller CA and Miller DM: Mithramycin inhibits Sp1 binding and selectively inhibits transcriptional activity of the dihydrofolate reductase gene in vitro and in vivo. J Clin Invest. 88:1613–1621. 1991. View Article : Google Scholar : PubMed/NCBI
25	Van Dyke MW and Dervan PB: Chromomycin, mithramycin and olivomycin binding sites on heterogeneous deoxyribonucleic acid. Footprinting with (methidiumpropyl-EDTA) iron (II). Biochemistry. 22:2373–2377. 1983. View Article : Google Scholar : PubMed/NCBI
26	Remsing LL, Bahadori HR, Carbone GM, McGuffie EM, Catapano CV and Rohr J: Inhibition of c-src transcription by mithramycin: Structure-activity relationships of biosynthetically produced mithramycin analogues using the c-src promoter as target. Biochemistry. 42:8313–8324. 2003. View Article : Google Scholar : PubMed/NCBI