Ukr.Biochem.J. 2017; Volume 89, Issue 5, Sep-Oct, pp. 40-51

doi: https://doi.org/10.15407/ubj89.05.040

Expression of tumor growth related genes in IRE1 knockdown U87 glioma cells: effect of hypoxia

O. H. Minchenko1, O. Y. Luzina1, O. S. Hnatiuk1,
D. O. Minchenko1,2, I. A. Garmash1, O. O. Ratushna1

1Palladin Institute of Biochemistry,  National Academy of Sciences of Ukraine, Kyiv;
e-mail: ominchenko@yahoo.com;
2Bohomolets National Medical University, Kyiv, Ukraine

We have studied the effect of IRE1 signaling enzyme knockdown as well as hypoxia on the expression of genes encoding the important tumor growth related proteins (BRCA1, DEK, BCL2L1, COL6A1, TPD52, HOMER3, and GNPDA1) in U87 glioma cells. It was shown that the expression level of breast cancer 1 early onset (BRCA1) and tumor protein D52 (TPD52) mRNAs are strongly up-regulated in U87 glioma cells by down-regulation of IRE1 expression in comparison with the control cells. At the same time the expression level of collagen, type VI, alpha 1 (COL6A1), DEK oncogene (DEK), glucosamine-6-phosphate deaminase 1 (GNPDA1) and homer homolog 3 (HOMER3) was significantly down-regulated in glioma cells under these experimental conditions. It was also shown that hypoxia up-regulated the expression level of COL6A1 and TPD52 mRNAs and down-regulated – BRCA1, DEK, and GNPDA1 mRNAs in control glioma cells and that down-regulation of IRE1, which control cell proliferation and tumor growth, modified the effect of hypoxia on the expression of COL6A1, DEK, BCL2L1, HOMER3, and GNPDA1 genes. The present study demonstrated that hypoxia affected the expression of most studied genes in IRE1-dependent manner.

Keywords: , , , , , , ,


References:

  1. Moenner M, Pluquet O, Bouchecareilh M, Chevet E. Integrated endoplasmic reticulum stress responses in cancer. Cancer Res. 2007 Nov 15;67(22):10631-4. PubMed, CrossRef
  2. Malhotra JD, Kaufman RJ. ER stress and its functional link to mitochondria: role in cell survival and death. Cold Spring Harb Perspect Biol. 2011 Sep 1;3(9):a004424. PubMed, PubMedCentral, CrossRef
  3. Jäger R, Bertrand MJ, Gorman AM, Vandenabeele P, Samali A. The unfolded protein response at the crossroads of cellular life and death during endoplasmic reticulum stress. Biol Cell. 2012 May;104(5):259-70. PubMed, CrossRef
  4. Auf G, Jabouille A, Guérit S, Pineau R, Delugin M, Bouchecareilh M, Magnin N, Favereaux A, Maitre M, Gaiser T, von Deimling A, Czabanka M, Vajkoczy P, Chevet E, Bikfalvi A, Moenner M. Inositol-requiring enzyme 1alpha is a key regulator of angiogenesis and invasion in malignant glioma. Proc Natl Acad Sci USA. 2010 Aug 31;107(35):15553-8.  PubMed, PubMedCentral, CrossRef
  5. Fujita A, Sato JR, Festa F, Gomes LR, Oba-Shinjo SM, Marie SK, Ferreira CE, Sogayar MC. Identification of COL6A1 as a differentially expressed gene in human astrocytomas. Genet Mol Res. 2008 Apr 22;7(2):371-8. PubMed, CrossRef
  6. Minchenko DO, Riabovol OO, Tsymbal DO, Ratushna OO, Minchenko OH. Inhibition of IRE1 signaling affects the expression of genes encoded glucocorticoid receptor and some related factors and their hypoxic regulation in U87 glioma cells. Endocr Regul. 2016 Jul;50(3):127-36. PubMed, CrossRef
  7. Auf G, Jabouille A, Delugin M, Guérit S, Pineau R, North S, Platonova N, Maitre M, Favereaux A, Vajkoczy P, Seno M, Bikfalvi A, Minchenko D, Minchenko O, Moenner M. High epiregulin expression in human U87 glioma cells relies on IRE1α and promotes autocrine growth through EGF receptor. BMC Cancer. 2013 Dec 13;13:597.  PubMed, PubMedCentral, CrossRef
  8. Pluquet O, Dejeans N, Chevet E. Watching the clock: endoplasmic reticulum-mediated control of circadian rhythms in cancer. Ann Med. 2014 Jun;46(4):233-43.  PubMed, CrossRef
  9. Chevet E, Hetz C, Samali A. Endoplasmic reticulum stress-activated cell reprogramming in oncogenesis. Cancer Discov. 2015 Jun;5(6):586-97. PubMed, CrossRef
  10. Yakkioui Y, Temel Y, Chevet E, Negroni L. Integrated and quantitative proteomics of human tumors. Methods Enzymol. 2017;586:229-246.  PubMed, CrossRef
  11. Minchenko OH, Kryvdiuk IV, Riabovol OO, Minchenko DO, Danilovskyi SV, Ratushna OO. Inhibition of IRE1 modifies the hypoxic regulation of GADD family gene expressions in U87 glioma cells. Ukr Biochem J. 2016; 88 (2): 25-34. CrossRef
  12. Minchenko OH, Tsymbal DO, Minchenko DO, Riabovol OO, Ratushna OO, Karbovskyi LL. Hypoxic regulation of the expression of cell proliferation related genes in U87 glioma cells upon inhibition of IRE1 signaling enzyme. Ukr Biochem J. 2016 Jan-Feb; 88(1): 11-21. CrossRef
  13. Minchenko DO, Riabovol OO, Ratushna OO, Minchenko OH. Hypoxic regulation of the expression of genes encoded estrogen related proteins in U87 glioma cells: effect of IRE1 inhibition. Endocr Regul. 2017 Jan 1;51(1):8-19. PubMed, CrossRef
  14. Obacz J, Avril T, Le Reste PJ, Urra H, Quillien V, Hetz C, Chevet E. Endoplasmic reticulum proteostasis in glioblastoma-From molecular mechanisms to therapeutic perspectives. Sci Signal. 2017 Mar 14;10(470). pii: eaal2323. PubMed, CrossRef
  15. Kaur B, Khwaja FW, Severson EA, Matheny SL, Brat DJ, Van Meir EG. Hypoxia and the hypoxia-inducible-factor pathway in glioma growth and angiogenesis. Neuro Oncol. 2005 Apr;7(2):134-53. PubMed, PubMedCentral, CrossRef
  16. Lenihan CR, Taylor CT. The impact of hypoxia on cell death pathways. Biochem Soc Trans. 2013 Apr;41(2):657-63.  PubMedCrossRef
  17. Hetz C, Chevet E, Harding HP. Targeting the unfolded protein response in disease. Nat Rev Drug Discov. 2013 Sep;12(9):703-19.  PubMed, CrossRef
  18. Manié SN, Lebeau J, Chevet E. Cellular mechanisms of endoplasmic reticulum stress signaling in health and disease. 3. Orchestrating the unfolded protein response in oncogenesis: an update. Am J Physiol Cell Physiol. 2014 Nov 15;307(10):C901-7.  PubMed, CrossRef
  19. Minchenko DO, Kharkova AP, Halkin OV, Karbovskyi LL, Minchenko OH. Effect of hypoxia on the expression of genes encoding insulin-like growth factors and some related proteins in U87 glioma cells without IRE1 function. Endocr Regul. 2016 Apr;50(2):43-54.  PubMed, CrossRef
  20. Minchenko OH, Kryvdiuk IV, Minchenko DO, Riabovol OO, Halkin OV. Inhibition of IRE1 signaling affects expression of a subset genes encoding for TNF-related factors and receptors and modifies their hypoxic regulation in U87 glioma cells. Endoplasm Reticul Stress Dis. 2016; 3(1): 1-15.  CrossRef
  21. Holt JT, Thompson ME, Szabo C, Robinson-Benion C, Arteaga CL, King MC, Jensen RA. Growth retardation and tumour inhibition by BRCA1. Nat Genet. 1996 Mar;12(3):298-302. PubMed, CrossRef
  22. Fujita A, Sato JR, Festa F, Gomes LR, Oba-Shinjo SM, Marie SK, Ferreira CE, Sogayar MC. Identification of COL6A1 as a differentially expressed gene in human astrocytomas. Genet Mol Res. 2008 Apr 22;7(2):371-8. PubMed, CrossRef
  23. Fan NJ, Gao CF, Wang CS, Zhao G, Lv JJ, Wang XL, Chu GH, Yin J, Li DH, Chen X, Yuan XT, Meng NL. Identification of the up-regulation of TP-alpha, collagen alpha-1(VI) chain, and S100A9 in esophageal squamous cell carcinoma by a proteomic method. J Proteomics. 2012 Jul 16;75(13):3977-86. PubMed, CrossRef
  24. Zhao Z, Liu H, Hou J, Li T, Du X, Zhao X, Xu W, Xu W, Chang J. Tumor Protein D52 (TPD52) Inhibits Growth and Metastasis in Renal Cell Carcinoma Cells Through the PI3K/Akt Signaling Pathway. Oncol Res. 2017 May 24;25(5):773-779. PubMed, CrossRef
  25. Yu L, Huang X, Zhang W, Zhao H, Wu G, Lv F, Shi L, Teng Y. Critical role of DEK and its regulation in tumorigenesis and metastasis of hepatocellular carcinoma. Oncotarget. 2016 May 3;7(18):26844-55. PubMed, PubMedCentral, CrossRef
  26. Shen TY, Mei LL, Qiu YT, Shi ZZ. Identification of candidate target genes of genomic aberrations in esophageal squamous cell carcinoma. Oncol Lett. 2016 Oct;12(4):2956-2961. PubMed, PubMedCentral, CrossRef
  27. Oikari S, Makkonen K, Deen AJ, Tyni I, Kärnä R, Tammi RH, Tammi MI. Hexosamine biosynthesis in keratinocytes: roles of GFAT and GNPDA enzymes in the maintenance of UDP-GlcNAc content and hyaluronan synthesis. Glycobiology. 2016 Jul;26(7):710-22. PubMed, CrossRef
  28. Minchenko DO, Danilovskyi SV, Kryvdiuk IV, Bakalets TV, Lypova NM, Karbovskyi LL, Minchenko OH. Inhibition of ERN1 modifies the hypoxic regulation of the expression of TP53-related genes in U87 glioma cells. Endoplasm Reticul Stress Dis. 2014; 1(1): 18-26.  CrossRef
  29. Bochkov VN, Philippova M, Oskolkova O, Kadl A, Furnkranz A, Karabeg E, Afonyushkin T, Gruber F, Breuss J, Minchenko A, Mechtcheriakova D, Hohensinner P, Rychli K, Wojta J, Resink T, Erne P, Binder BR, Leitinger N. Oxidized phospholipids stimulate angiogenesis via autocrine mechanisms, implicating a nvel role for lipid oxidation in the evolution of atherosclerotic lesions. Circ Res. 2006; 99(8): 900-908. CrossRef
  30. Minchenko OH, Tsymbal DO, Minchenko DO, Kubaychuk OO. Hypoxic regulation of MYBL1, MEST, TCF3, TCF8, GTF2B, GTF2F2 and SNAI2 genes expression in U87 glioma cells upon IRE1 inhibition. Ukr Biochem J. 2016; 88(6): 52-62. CrossRef
  31. Denko NC. Hypoxia, HIF1 and glucose metabolism in the solid tumour. Nat Rev Cancer. 2008 Sep;8(9):705-13. PubMed, CrossRef
  32. Minchenko OH, Tsymbal DO, Minchenko DO, Riabovol OO, Halkin OV, Ratushna OO.  IRE-1α regulates expression of ubiquitin specific peptidases during hypoxic response in U87 glioma cells. Endoplasm Reticul Stress Dis. 2016; 3(1): 50-62.  CrossRef
  33. Minchenko DO, Kharkova AP, Karbovskyi LL, Minchenko OH. Expression of insulin-like growth factor binding protein genes and its hypoxic regulation in U87 glioma cells depends on ERN1 mediated signaling pathway of endoplasmic reticulum stress. Endocr Regul. 2015 Apr;49(2):73-83. PubMed, CrossRef
  34. Minchenko OH, Riabovol OO, Tsymbal DO, Minchenko DO, Ratushna OO. Effect of hypoxia on the expression of nuclear genes encoding mitochondrial proteins in U87 glioma cells. Ukr Biochem J. 2016; 88(3): 54-65. CrossRef
  35. Chiavarina B, Nokin MJ, Bellier J, Durieux F, Bletard N, Sherer F, Lovinfosse P, Peulen O, Verset L, Dehon R, Demetter P, Turtoi A, Uchida K, Goldman S, Hustinx R, Delvenne P, Castronovo V, Bellahcène A. Methylglyoxal-Mediated Stress Correlates with High Metabolic Activity and Promotes Tumor Growth in Colorectal Cancer. Int J Mol Sci. 2017 Jan 21;18(1). pii: E213.  PubMed, PubMedCentral, CrossRef
  36. Hutschenreuther A, Bigl M, Hemdan NY, Debebe T, Gaunitz F, Birkenmeier G. Modulation of GLO1 Expression Affects Malignant Properties of Cells. Int J Mol Sci. 2016 Dec 18;17(12). pii: E2133.  PubMed, PubMedCentral, CrossRef

Creative CommonsThis work is licensed under a Creative Commons Attribution 4.0 International License.