DOI QR코드

DOI QR Code

Microarray Analysis of the Hypoxia-induced Gene Expression Profile in Malignant C6 Glioma Cells

  • Huang, Xiao-Dong ;
  • Wang, Ze-Fen ;
  • Dai, Li-Ming ;
  • Li, Zhi-Qiang
  • Published : 2012.09.30

Abstract

Hypoxia is commonly featured during glioma growth and plays an important role in the processes underlying tumor progression to increasing malignancy. Here we compared the gene expression profiles of rat C6 malignant glioma cells under normoxic and hypoxic conditions by cDNA microarray analysis. Compared to normoxic culture conditions, 180 genes were up-regulated and 67 genes were down-regulated under hypoxia mimicked by $CoCl_2$ treatment. These differentially expressed genes were involved in mutiple biological functions including development and differentiation, immune and stress response, metabolic process, and cellular physiological response. It was found that hypoxia significantly regulated genes involved in regulation of glycolysis and cell differentiation, as well as intracellular signalling pathways related to Notch and focal adhesion, which are closely associated with tumor malignant growth. These results should facilitate investigation of the role of hypoxia in the glioma development and exploration of therapeutic targets for inhibition of glioma growth.

Keywords

Glioma;hypoxia;microarray;differentially expressed genes

References

  1. Bar EE, Lin A, Mahairaki V, et al (2010). Hypoxia increases the expression of stem-cell markers and promotes clonogenicity in glioblastoma neurospheres. Am J Pathol, 177, 1491-502. https://doi.org/10.2353/ajpath.2010.091021
  2. Cooper LA, Gutman DA, Long Q, et al (2010). The proneural molecular signature is enriched in oligodendrogliomas and predicts improved survival among diffuse gliomas. PLoS One, 5, e12548. https://doi.org/10.1371/journal.pone.0012548
  3. Dai M, Cui P, Yu M, et al (2008). Melatonin modulates the expression of VEGF and HIF-1 alpha induced by CoCl2 in cultured cancer cells. J Pineal Res, 44, 121-6. https://doi.org/10.1111/j.1600-079X.2007.00498.x
  4. Di Matteo P, Arrigoni GL, Alberici L, et al (2011). Enhanced expression of CD13 in vessels of inflammatory and neoplastic tissues. J Histochem Cytochem, 59, 47-59. https://doi.org/10.1369/jhc.2010.956644
  5. Du R, Lu KV, Petritsch C, et al (2008). HIF-1 alpha induces the recruitment of bone marrow-derived vascular modulatory cells to regulate tumor angiogenesis and invasion. Cancer Cell, 13, 206-20. https://doi.org/10.1016/j.ccr.2008.01.034
  6. Eckerich C, Zapf S, Fillbrandt R, et al (2007). Hypoxia can induce c-Met expression in glioma cells and enhance SF/ HGF-induced cell migration. Int J Cancer, 121, 276-83. https://doi.org/10.1002/ijc.22679
  7. Fujiwara S, Nakagawa K, Harada H, et al (2007). Silencing hypoxia-inducible factor-1${\alpha}$ inhibits cell migration and invasion under hypoxic environment in malignant gliomas. Int J Oncol, 30, 793-802.
  8. Gonzalez A, Kageyama R (2010). Automatic reconstruction of the mouse segmentation network from an experimental evidence database.Biosystems, 102, 16-21. https://doi.org/10.1016/j.biosystems.2010.07.013
  9. Ha E, Han E, Park HJ, et al (2006). Microarray analysis of transcription factor gene expression in melatonin-treated human peripheral blood mononuclear cells. J Pineal Res, 40, 305-11. https://doi.org/10.1111/j.1600-079X.2006.00317.x
  10. Henke RM, Meredith DM, Borromeo MD, et al (2009).Ascl1 and Neurog2 form novel complexes and regulate Delta-like3 (Dll3) expression in the neural tube. Dev Biol, 328, 529-40. https://doi.org/10.1016/j.ydbio.2009.01.007
  11. Iizuka K, Horikawa Y (2008). ChREBP: a glucose-activated transcription factor involved in the development of metabolic syndrome. Endocr J, 55, 617-24. https://doi.org/10.1507/endocrj.K07E-110
  12. Jones DT, Mulholland SA, Pearson DM, et al (2011). Adult grade II diffuse astrocytomas are genetically distinct from and more aggressive than their paediatric counterparts. Acta Neuropathol, 121, 753-61. https://doi.org/10.1007/s00401-011-0810-6
  13. Kern W, Kohlmann A, Schoch C, et al (2006). Comparison of mRNA abundance quantified by gene expression profiling and percentage of positive cells using immunophenotyping for diagnostic antigens in acute and chronic leukemias. Cancer, 107, 2401-7. https://doi.org/10.1002/cncr.22251
  14. Kolenda J, Jensen SS, Aaberg-Jessen C, et al (2011). Effects of hypoxia on expression of a panel of stem cell and chemoresistance markers in glioblastoma-derived spheroids. J Neurooncol, 103, 43-58. https://doi.org/10.1007/s11060-010-0357-8
  15. Kumar Y, Mazurek S, Yang S, et al (2010). In vivo factors influencing tumour M2-pyruvate kinase level in human pancreatic cancer cell lines. Tumour Biol, 31, 69-77. https://doi.org/10.1007/s13277-009-0010-3
  16. Li Z, Wang J, Gong L, et al (2011). Correlation of Delta-like Ligand 4 (DLL4) with VEGF and HIF-1alpha Expression in Human Glioma. Asian Pac J Cancer Prev, 12, 215-8.
  17. Luo W, Hu H, Chang R, et al (2011). Pyruvate kinase M2 is a PHD3-stimulated coactivator for hypoxia-inducible factor 1. Cell, 145, 732-44. https://doi.org/10.1016/j.cell.2011.03.054
  18. Mawrin C, Wolke C, Haase D, et al (2010). Reduced activity of CD13/ aminopeptidase N (APN) in aggressive meningiomas is associated with increased levels of SPARC. Brain Pathol, 20, 200-10. https://doi.org/10.1111/j.1750-3639.2009.00267.x
  19. Onishi M, Ichikawa T, Kurozumi K, et al (2011). Angiogenesis and invasion in glioma. Brain Tumor Pathol, 28, 13-24. https://doi.org/10.1007/s10014-010-0007-z
  20. Phillips HS, Kharbanda S, Chen R, et al (2006). Molecular subclasses of high-grade glioma predict prognosis, delineate a pattern of disease progression, and resemble stages in neurogenesis. Cancer Cell, 9, 157-73. https://doi.org/10.1016/j.ccr.2006.02.019
  21. Potolicchio I, Carven GJ, Xu X, et al (2005). Proteomic analysis of microglia-derived exosomes: metabolic role of the aminopeptidase CD13 in neuropeptide catabolism. J Immunol, 175, 2237-43. https://doi.org/10.4049/jimmunol.175.4.2237
  22. Ravanpay AC, Hansen SJ, Olson JM (2010). Transcriptional inhibition of REST by NeuroD2 during neuronal differentiation. Mol Cell Neurosci, 44, 178-89. https://doi.org/10.1016/j.mcn.2010.03.006
  23. Rostomily RC, Bermingham-McDonogh O, Berger MS, et al (1997). Expression of neurogenic basic helix-loop-helix genes in primitive neuroectodermal tumors. Cancer Res, 57, 3526-31.
  24. Shimizu T, Uehara T, Nomura Y (2004). Possible involvement of pyruvate kinase in acquisition of tolerance to hypoxic stress in glial cells. J Neurochem, 91, 167-75. https://doi.org/10.1111/j.1471-4159.2004.02702.x
  25. Vlashi E, Lagadec C, Vergnes L, et al (2011). Metabolic state of glioma stem cells and nontumorigenic cells.Proc Natl Acad Sci, 108, 16062-7. https://doi.org/10.1073/pnas.1106704108
  26. Westerman BA, Poutsma A, Maruyama K, et al (2002). The proneural genes NEUROD1 and NEUROD2 are expressed during human trophoblast invasion. Mech Dev, 113, 85-90. https://doi.org/10.1016/S0925-4773(01)00665-7
  27. Winnicka B, O'Conor C, Schacke W, et al (2010). CD13 is dispensable for normal hematopoiesis and myeloid cell functions in the mouse. J Leukoc Biol, 88, 347-59. https://doi.org/10.1189/jlb.0210065
  28. Xu X, Li Z, Wen Z (2010). Glioma-conditioned medium blocks endothelial cells' apoptosis induced by hypoxia and promotes its angiogenesis via up-regulation of uPA/ uPAR. Chin J Cancer Res, 21, 119-25.

Cited by

  1. HIF-1α and GLUT1 Gene Expression is Associated with Chemoresistance of Acute Myeloid Leukemia vol.15, pp.4, 2014, https://doi.org/10.7314/APJCP.2014.15.4.1823
  2. A Combined Gene Signature of Hypoxia and Notch Pathway in Human Glioblastoma and Its Prognostic Relevance vol.10, pp.3, 2015, https://doi.org/10.1371/journal.pone.0118201
  3. Involvement of ROS-alpha v beta 3 integrin-FAK/Pyk2 in the inhibitory effect of melatonin on U251 glioma cell migration and invasion under hypoxia vol.13, pp.1, 2015, https://doi.org/10.1186/s12967-015-0454-8
  4. Hypoxia Strongly Affects Mitochondrial Ribosomal Proteins and Translocases, as Shown by Quantitative Proteomics of HeLa Cells vol.2015, pp.2090-2174, 2015, https://doi.org/10.1155/2015/678527
  5. Peritumoral edema on magnetic resonance imaging predicts a poor clinical outcome in malignant glioma pp.1792-1082, 2015, https://doi.org/10.3892/ol.2015.3639
  6. Time-series analysis in imatinib-resistant chronic myeloid leukemia K562-cells under different drug treatments vol.37, pp.4, 2017, https://doi.org/10.1007/s11596-017-1781-1
  7. Hypoxia and Selective Autophagy in Cancer Development and Therapy vol.6, pp.2296-634X, 2018, https://doi.org/10.3389/fcell.2018.00104