Identification of Novel Hypoxia Response Genes in Human Glioma Cell Line A172

Document Type: Original Article

Authors

1 1Department of Medical Genetics, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

2 Department of Clinical Biochemistry, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

3 of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

4 1Department of Medical Genetics, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Ira

5 Department of Clinical Biochemistry, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

Abstract

 

Objective(s):
Hypoxia is a serious challenge for treatment of solid tumors. This condition has been manifested to exert significant therapeutic effects on glioblastoma multiform or (WHO) astrocytoma grade IV. Hypoxia contributes numerous changes in cellular mechanisms such as angiogenesis, metastasis and apoptosis evasion. Furthermore, in molecular level, hypoxia can cause induction of DNA breaks in tumor cells. Identification of mechanisms responsible for these effects can lead to designing more efficient therapeutic strategies against tumor progression which results in improvement of patient prognosis.
 
Materials and Methods:
In order to identify more hypoxia regulated genes which may have a role in glioblastoma progression, cDNA-AFLP was optimized as a Differential display method which is able to identify and isolate transcripts with no prior sequence knowledge.
Results:
Using this method, the current study identified 120 Transcription Derived Fragments (TDFs) which were completely differentially regulated in response to hypoxia. By sequence homology searching, the current study could detect 22 completely differentially regulated known genes and two unknown sequence matching with two chromosome contig and four sequence matches with some Expressed Sequence Tags (ESTs).
Conclusion:
Further characterizing of these genes may help to achieve better understanding of hypoxia mediated phenotype change in tumor cells.

Keywords


1. Kizaka-Kondoh S, Inoue M, Harada H, Hiraoka M. Tumor hypoxia: a target for selective cancer therapy. Cancer Sci 2003; 94:1021-1028.

2. Anastasiadis AG, Stisser BC, Ghafar MA, Burchardt M, Buttyan R. Tumor hypoxia and the progression of prostate cancer. Current Urol Reports 2002; 3:222-228.

3. Jiang J, Tang YL, Liang XH. EMT: a new vision of hypoxia promoting cancer progression. Cancer Biol Ther 2011; 11:714-723.

4. Osinsky S, Zavelevich M, Vaupel P. Tumor hypoxia and malignant progression. Exp Oncol 2009; 31:80-86.

5. JM. B. Tumor hypoxia in cancer therapy. Methods Enzymol 2007; 435:297-321.

6. Duffy JP, Eibl G, Reber HA, Hines OJ. Influence of hypoxia and neoangiogenesis on the growth of pancreatic cancer. Mol Cancer 2003; 2:12.

7. Hoelzinger DB, Mariani L, Weis J, Woyke T, Berens TJ, McDonough WS, et al. Gene Expression Profile of Glioblastoma Multiforme Invasive Phenotype Points to New Therapeutic Targets. Neoplasia 2005; 7:7-16.

8. Argyriou AA, Giannopoulou E HPK. Angiogenesis and anti-angiogenic molecularly targeted therapies in malignant fgiomas. Oncology 2009; 77:1-11.

9. Liao D, Johnson RS. Hypoxia: a key regulator of angiogenesis in cancer. Cancer MetastasisRrev 200; 7 26:281-90.

10. Kalliomaki TM, McCallum G, Lunt SJ, Wells PG, Hill RP. Analysis of the effects of exposure to acute hypoxia on oxidative lesions and tumour progression in a transgenic mouse breast cancer model. BMC cancer 2008; 8:151.

11. Zhou Y, Zhou Y, Shingu T, Feng L, Chen Z, Ogasawara M, et al. Metabolic alterations in highly tumorigenic glioblastoma cells: preference for hypoxia and high dependency on glycolysis. J Biologic Chemi 2011; 286:32843-3253.

12. Zhou J, Schmid T, Schnitzer S, Brune B. Tumor hypoxia and cancer progression. Cancer lett 2006; 237:10-21.

13. Avni R, Cohen BM N. Hypoxic stress and cancer: imaging the axis of evil in tumor metastasis. NMR Biomed 2011; 24:569-581.

14. Amberger-Murphy V. Hypoxia helps glioma to fight therapy. Curr Cancer Drug Targets 2009; 9:381-390.

15. Denko NC, Fontana LA, Hudson KM, Sutphin PD, Raychaudhuri S, Altman R, et al. Investigating hypoxic tumor physiology through gene expression patterns. Oncogene 2003; 22:5907-5914.

16. Casero RA, Pegg AE. Spermidine/spermine N1-acetyltransferase--the turning point in polyamine metabolism. Faseb J 1993; 7:653-661.

17. Tucker JM, Murphy JT, Kisiel N, Diegelman P, Barbour KW, Davis C, et al. Potent modulation of intestinal tumorigenesis in Apcmin/+ mice by the polyamine catabolic enzyme spermidine/spermine N1-acetyltransferase. Cancer Res 2005; 65:5390-538.

18. Anthony E P, Michael AJ. Spermine synthase. Cell Mol Life Sci 2011; 67:113-121.

19. Baillon JG, Kolb M, Mamont PS. Inhibition of mammalian spermine synthase by N-alkylated-1, 3-diaminopropane derivatives in vitro and in cultured rat hepatoma cells. Eur J Biochem FEBS 1989; 179:17-21.

20. Clarkson AN, Liu H, Pearson L, Kapoor M, Harrison JC, Sammut IA, et al. Neuroprotective effects of spermine following hypoxic-ischemic-induced brain damage: a mechanistic study. Faseb J 2004; 18:1114-1116.

21. Thaker NG, Zhang F, McDonald PR, Shun TY, Lewen MD, Pollack IF, et al. Identification of survival genes in human glioblastoma cells by small interfering RNA screening. Mol Pharmacol 2009; 76:1246-1255.

22. Saletta F, Suryo Rahmanto Y, Richardson DR. The translational regulator EIF3a: the tricky EIF3 subunit! Biochim Biophys Acta 2010; 1806:275-286.

23. Hershey JW. Regulation of protein synthesis and the role of EIF3 in cancer. Braz J Med Biol Res 2010 ; 43:920-930.

24. Dong Z, Zhang JT. Initiation factor EIF3 and regulation of mRNA translation, cell growth, and cancer. Crit Rev Oncol Hematol 2006; 59:169-180.

25. Watkins SJ, Norbury CJ. Translation initiation and its deregulation during tumorigenesis. Br J Cancer 2002; 86:1023-1027.

26. Gorgoni B, Gray NK. The roles of cytoplasmic poly (A)-binding proteins in regulating gene expression: a developmental perspective. Brief Funct Genomict Proteomict 2004 3:125–141.

27. Lemay JF, Lemieux C, St-Andre O, Bachand F. Crossing the borders: poly (A)-binding proteins working on both sides of the fence. RNA Biol 2011; 7:291-295.

28. Thangima Zannat M, Bhattacharjee RB, Bag J. Depletion of cellular poly (A) binding protein prevents protein synthesis and leads to apoptosis in HeLa cells. Biochem Biophys Res Commun 2011; 408:375-381.

29. Zekri L, Huntzinger E, Heimstädt S, Izaurralde E. The Silencing Domain of GW182 Interacts with PABPC1 To Promote Translational Repression and Degradation of MicroRNA Targets and Is Required for Target Release. Mol Cell Biol 2009; 29:6220-6231.

30. Kudlinzki D, Nagel C, Ficner R. Crystallization and preliminary X-ray diffraction analysis of the C-terminal domain of the human spliceosomal DExD/H-box protein hPrp22. Acta Crystallogr Sect F Struct Biol Cryst Commun 2009; 65:956-958.

31. Ono Y, Ohno M, Shimura Y. Identification of a putative RNA helicase (HRH1), a human homolog of yeast Prp22. Mol Cell Biol 1994; 14:7611-7620.

32. Tan S, Guschin D, Davalos A, Lee YL, Snowden AW, Jouvenot Y, et al. Zinc-finger protein-targeted gene regulation: genomewide single gene specificity. Proc Natl Acad Sci U S A 2003; 100:11997-2002.

33. Li Z, Wang D, Na X, Schoen SR, Messing EM, Wu G. The VHL protein recruits a novel KRAB-A domain protein to repress HIF-1alpha transcriptional activity. EMBO J 2003; 22:1857-1867.

34. Mao XG, Yan M, Xue XY, Zhang X, Ren HG, Guo G, et al. Overexpression of ZNF217 in glioblastoma contributes to the maintenance of glioma stem cells regulated by hypoxia-inducible factors. Laboratory investigation.J Tech Methods Pathol 2011; 91:1068-1078.

35. Goodchild RE, Dauer WT. The AAA+ protein torsinA interacts with a conserved domain present in LAP1 and a novel ER protein. J Cell Biol 2005; 168:855-862.

36. Vander Heyden AB, Naismith TV, Snapp EL, Hodzic D, Hanson PI. LULL1 retargets TorsinA to the nuclear envelope revealing an activity that is impaired by the DYT1 dystonia mutation. Mol Biol Cell 2009; 20:2661-2672.

Transcriptome Changes in Hypoxia Fatemeh Baghbani et al

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671

37. Niikura T, Tajima H, Kita Y. Neuronal cell death in Alzheimer's disease and a neuroprotective factor, humanin. Curr Neuropharmacol 2006; 4:139-1347.

38/. Xu X, Chua CC, Gao J, Chua KW, Wang H, Hamdy RC, et al. Neuroprotective effect of humanin on cerebral ischemia/reperfusion injury is mediated by a PI3K/Akt pathway. Brain Res 2008; 1227:12-18.

39. Kariya S, Hirano M, Furiya Y, Ueno S. Effect of humanin on decreased ATP levels of human lymphocytes harboring A3243G mutant mitochondrial DNA. Neuropeptides 2005; 39:97-101.

40. Zapala B, Staszel T, Kiec-Wilk B, Polus A, Knapp A, Wybranska I, et al. Humanin and its derivatives as peptides with potential antiapoptotic and confirmed neuroprotective activities. Przegl Lek 2011; 68:372-377.

41. Kariya S, Hirano M, Furiya Y, Sugie K, Ueno S. Humanin detected in skeletal muscles of MELAS patients: a possible new therapeutic agent. Acta Neuropathol 2005; 109:367-372.

42. Hashimoto Y, Suzuki H, Aiso S, Niikura T, Nishimoto I, Matsuoka M. Involvement of tyrosine kinases and STAT3 in Humanin-mediated neuroprotection. Life Sci 2005; 77:3092-3104.

43. Liston P, Fong WG, Kelly NL, Toji S, Miyazaki T, Conte D, et al. Identification of XAF1 as an antagonist of XIAP anti-Caspase activity. Nat Cell Biol 2001; 3:128-133.

44. Kashkar HX-linked Inhibitor of Apoptosis: A Chemoresistance Factor or a Hollow Promise. Clin Cancer Res 2010; 16:4496.

45. Galban S, Duckett CS. XIAP as an ubiquitin ligase in cellular signaling. Cell Death Differ 2010; 17:54-60.

46. Karmakar S, Olive MF, Banik NL, Ray SK.

Intracranial stereotaxic cannulation for development of orthotopic glioblastoma allograft in sprague-dawley rats and histoimmunopathological characterization of the brain tumor. Neurochem Res 2007; 32:2235–2242.

47. Chandrasekaran Y, McKee CM, Ye Y, Richburg JH. Influence of TRP53 status on FAS membrane localization, CFLAR (c-FLIP) ubiquitinylation, and sensitivity of GC-2spd (ts) cells to undergo FAS-mediated apoptosis. Biol Reprod 2006; 74:560-568.

48. Kawabata M, Kawabata T, Nishibori M. Role of recA/RAD51 family proteins in mammals. Acta Med Okayama 2005; 59:1-9.

49. Benson FE, Stasiak A, SC W. Purification and characterization of the human Rad51 protein, an analogue of E. coli RecA. EMBO J 1994; 13:5764- 5771.

50. Jiao L, Hassan MM, Bondy ML, Wolff RA, Evans DB, Abbruzzese JL, et al. XRCC2 and XRCC3 gene polymorphism and risk of pancreatic cancer. Am J Gastroenterol 2008; 103:360-367.

51. Kondo N, Takahashi A, Mori E, Ohnishi K, McKinnon PJ, Sakaki T, et al. DNA ligase IV as a new molecular target for temozolomide. Biochem Biophys Res Commun 2009; 387:656-660.

52. Donkor FF, Monnich M, Czirr E, Hollemann T, Hoyer-Fender S. Outer dense fibre protein 2 (ODF2) is a self-interacting centrosomal protein with affinity for microtubules. J Cell Sci 2004; 117:4643-4651.

53. Vos P HR, Bleeker M, Reijans M, van de Lee T, Hornes M, Frijters APJ, et al. AFLP: a new technique for DNA fingerprinting. Nucl Acids Res 1995; 23:4407-4411.