The Relationship between the Expression of Small Heat-Shock Proteins and Suppression of OCT4B1

Document Type: Original Article

Authors

1 Assistant Professor of Molecular Genetics, Molecular Medicine Research Center, Research Institute of Basic Medical Sciences and Department of Clinical Biochemistry Rafsanjan University of Medical Sciences, Rafsanjan, Iran

2 MSc of Molecular Genetics, Molecular Medicine Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, Iran

3 Professor of Hematology, Molecular Medicine Research Center, Research Institute of Basic Medical Sciences and Department of Immunology, Rafsanjan University of Medical Sciences, Rafsanjan, Iran

4 Professor of Clinical Biochemistry, Molecular Medicine Research Center, Research Institute of Basic Medical Sciences and Department of Clinical Biochemistry Rafsanjan University of Medical Sciences, Rafsanjan, Iran

5 MSc of Immunology, Molecular Medicine Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, Iran

6 MSc of Biochemistry, Molecular Medicine Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, Iran

Abstract

Background: OCT4B1, a variant of OCT4, is expressed in both cancer cells and tissues. This variant has a main role in the regulation of both apoptotic and stress (heat-shock proteins) pathways. The aim of this study was to investigate the effects of OCT4B1 silencing on the expression of small heat-shock proteins (sHSPs)in three human tumor cell lines.
Methods:AGS (gastric adenocarcinoma), 5637 (bladder tumor) and U-87MG (brain tumor) cell lines were transfected with specific OCT4B1 siRNA (test group) and scramble siRNA (control group), using siRNA and Lipofectamine. Real-Time PCR Array technique was applied and the fold changes were calculated using RT2 Profiler PCR Array Data Analysis version 3.5.
Results: It was revealed that HSPB1, HSPB6 and HSPE1 were down-regulated in all three studied tumor cell lines and HSPB2, HSPB7 and HSPB8 were down-regulated in two of three studied tumor cell lines (AGS and 5637). It was also revealed that HSPB3 was down-regulated in 5637 cell line and up-regulated in AGS and U87MG cell lines.
Conclusion: According to the results, it may be concluded that there is a direct relationship between OCT4B1 and sHSPs gene family expression. Thus, suppression of OCT4B1 may be considered in cancer therapy/research.

Keywords


  1. Scholer HR, Ruppert S, Suzuki N, Chowdhury K, Gruss P. New type of POU domain in germ line-specific protein Oct-4. Nature 1990; 344(6265):435-9.
  2. Lee J, Kim HK, Rho JY, Han YM, Kim J. The human OCT-4 isoforms differ in their ability to confer self-renewal. J Biol Chem 2006; 281(44):33554-65.
  3. Mirzaei MR, Najafi A, Arababadi MK, Asadi MH, Mowla SJ. Altered expression of apoptotic genes in response to OCT4B1 suppression in human tumor cell lines. Tumor Biology 2014; 35(10):9999-10009.
  4. Clarke MF, Becker MW. Stem cells: the real culprits in cancer? Sci Am 2006; 295(1):52-9.
  5. Clarke MF, Fuller M. Stem cells and cancer: two faces of eve. Cell 2006; 124(6):1111-5.
  6. Reya T, Morrison SJ, Clarke MF, Weissman IL. Stem cells, cancer, and cancer stem cells. Nature 2001; 414(6859):105-11.
  7. Prud'homme GJ. Cancer stem cells and novel targets for antitumor strategies. Curr Pharm Des 2012; 18(19):2838-49.
  8. Yasuda H, Tanaka K, Okita Y, Araki T, Saigusa S, Toiyama Y, et al. CD133, OCT4, and NANOG in ulcerative colitis-associated colorectal cancer. Oncol Lett 2011; 2(6):1065-71.
  9. Gao Y, Wang X, Han J, Xiao Z, Chen B, Su G, et al. The novel OCT4 spliced variant OCT4B1 can generate three protein isoforms by alternative splicing into OCT4B. J Genet Genomics 2010; 37(7):461-5.
  10. Atlasi Y, Mowla SJ, Ziaee SA, Gokhale PJ, Andrews PW. OCT4 spliced variants are differentially expressed in human pluripotent and nonpluripotent cells. Stem Cells 2008; 26(12):3068-74.
  11. Mirzaei MR, Mahmoodi M, Hassanshahi G, Ahmadi Z. Down-regulation of anti-apoptotic genes in tumor cell lines is facilitated by suppression of OCT4B1. Adv Med Sci 2017; 62(1):97-102.
  12. Bagrezaei F, Hassanshahi G, Mahmoodi M, Khanamani Falahati-Pour S, Mirzaei MR. Expression of inhibitor of apoptosis gene family members in bladder cancer tissues and the 5637 tumor cell line. Asian Pac J Cancer Prev 2018; 19(2):529-32.
  13. Farashahi Yazd E, Rafiee MR, Soleimani M, Tavallaei M, Salmani MK, Mowla SJ. OCT4B1, a novel spliced variant of OCT4, generates a stable truncated protein with a potential role in stress response. Cancer Lett 2011; 309(2):170-5.
  14. Parcellier A, Gurbuxani S, Schmitt E, Solary E, Garrido C. Heat shock proteins, cellular chaperones that modulate mitochondrial cell death pathways. Biochem Biophys Res Commun 2003; 304(3):505-12.
  15. Mirzaei MR, Asadi M, Mowla SJ, Hassanshahi G, Ahmadi Z. Down-regulation of HSP40 gene family following OCT4B1 suppression in human tumor cell lines. Iran J Basic Med Sci 2016; 19(2):187-93.
  16. Gupta SC, Sharma A, Mishra M, Mishra RK, Chowdhuri DK. Heat shock proteins in toxicology: how close and how far? Life Sci 2010; 86(11-12):377-84.
  17. Schmitt E, Gehrmann M, Brunet M, Multhoff G, Garrido C. Intracellular and extracellular functions of heat shock proteins: repercussions in cancer therapy. J Leukoc Biol 2007; 81(1):15-27.
  18. Lanneau D, Brunet M, Frisan E, Solary E, Fontenay M, Garrido C. Heat shock proteins: essential proteins for apoptosis regulation. J Cell Mol Med 2008; 12(3):743-61.
  19. Ciocca DR, Calderwood SK. Heat shock proteins in cancer: diagnostic, prognostic, predictive, and treatment implications. Cell Stress Chaperones 2005; 10(2):86-103.
  20. Reed JC. Mechanisms of apoptosis avoidance in cancer. Curr Opin Oncol 1999; 11(1):68-75.
  21. Mirzaei MR, Kazemi Arababadi M, Asadi MH, Mowla SJ. Altered Expression of High Molecular Weight Heat Shock Proteins after OCT4B1 Suppression in Human Tumor Cell Lines. Cell J 2016; 17(4): 608–16.
  22. Momeni M, Reza Mirzaei M, Zainodini N, Hassanshahi G, Arababadi MK. MiR-143 induces expression of AIM2 and ASC in Jurkat cell line. Iran J Immunol 2013; 10(2):103-9.
  23. Cheng CF, Fan J, Fedesco M, Guan S, Li Y, Bandyopadhyay B, et al. Transforming growth factor alpha (TGFalpha)-stimulated secretion of HSP90alpha: using the receptor LRP-1/CD91 to promote human skin cell migration against a TGFbeta-rich environment during wound healing. Mol Cell Biol 2008; 28(10):3344-58.
  24. Centenera MM, Fitzpatrick AK, Tilley WD, Butler LM. Hsp90: still a viable target in prostate cancer. Biochim Biophys Acta 2013; 1835(2):211-8.
  25. Niknejad H, Yazdanpanah G, Mirmasoumi M, Abolghasemi H, Peirovi H, Ahmadiani A. Inhibition of HSP90 could be possible mechanism for anti-cancer property of amniotic membrane. Medical Hypotheses 2013; 81(5):862-5.
  26. Yu HJ, Chang YH, Pan CC. Prognostic significance of heat shock proteins in urothelial carcinoma of the urinary bladder. Histopathology 2013; 62(5):788-98.
  27. Asadi MH, Mowla SJ, Fathi F, Aleyasin A, Asadzadeh J, Atlasi Y. OCT4B1, a novel spliced variant of OCT4, is highly expressed in gastric cancer and acts as an antiapoptotic factor. Int J Cancer 2011; 128(11):2645-52.
  28. Asadzadeh J, Asadi MH, Shakhssalim N, Rafiee MR, Kalhor HR, Tavallaei M, et al. A plausible anti-apoptotic role of up-regulated OCT4B1 in bladder tumors. Urol J 2012; 9(3):574-80.