SIRT4 Overexpression Promotes the Inhibition of Cell Proliferation and Invasion in Prostate Cancer

Authors

  • Abdul-Nazif Mahmud  Department of Urology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, People's Republic of China
  • Feilun Cui  School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, People's Republic of China
  • Xue Bo  Department of General Surgery, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, People's Republic of China
  • Jianpeng Hu  Department of General Surgery, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, People's Republic of China
  • Tingjun Liu  Department of General Surgery, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, People's Republic of China
  • Muslimat Kehinde Adebis  Department of General Surgery, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, People's Republic of China
  • Said Abdulrahman Salim  Department of General Surgery, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, People's Republic of China
  • Aaron Gia Kanton  Department of General Surgery, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, People's Republic of China

DOI:

https://doi.org//10.32628/IJSRST207347

Keywords:

Cell Invasion, LNCaP cells, Prostate cancer, SIRT4 and Tumor suppressor

Abstract

Background: SIRT4 is among the few characterized individual sirtuin groups of nicotinamide adenine dinucleotide-dependent enzymes base in the mitochondria that facilitate several significant processes at the cellular level including stress response, metabolism and longevity. SIRT4 can suppress and inhibits the growth, proliferation and transformation of tumor cells such as colorectal and gastric tumors by suppressing glutamine anaplerosis, but there is no research that reveal the role and function SIRT4 plays in the development of prostate tumor.

Methods: Overexpression of SIRT4 in prostate cancer cell lines LNCaP was determined using RT-qPCR and Western blotting analyses. CCK-8 and transwell analysis were utilized to establish SIRT4 overexpression effects on cell proliferation and cell invasion respectively.

Results: This study first established SIRT4 overexpression in prostate cancer cell lines LNCaP, functional experiment such as CCK-8 assay reveals that, overexpression of SIRT4 suppressed cell proliferation. In addition, transwell assay reveals that, SIRT4 overexpression inhibits cell invasion.

Conclusions: This research findings reveals that, SIRT4 function to suppress prostate cancer cells by impeding the proliferation and invasion of LNCaP cells. SIRT4 may serve as a new treatment target for prostate tumor.

References

  1. F. Bray, J. Ferlay, I. Soerjomataram, R. L. Siegel, L. A. Torre, and A. Jemal, “Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries,” CA: a cancer journal for clinicians, 2018.
  2. R. L. Siegel, and K. D. Miller, “Cancer statistics, 2019,” vol. 69, no. 1, pp. 7-34, Jan, 2019.
  3. K. A. Cronin, A. J. Lake, S. Scott, R. L. Sherman, A. M. Noone, N. Howlader, S. J. Henley, R. N. Anderson, A. U. Firth, and J. Ma, “Annual Report to the Nation on the Status of Cancer, part I: National cancer statistics,” Cancer, 2018.
  4. H. Sun, D. Huang, G. Liu, F. Jian, J. Zhu, and L. Zhang, “sirT4 acts as a tumor suppressor in gastric cancer by inhibiting cell proliferation, migration, and invasion,” OncoTargets and therapy, vol. 11, pp. 3959, 2018.
  5. M. C. Haigis, R. Mostoslavsky, K. M. Haigis, K. Fahie, D. C. Christodoulou, A. J. Murphy, D. M. Valenzuela, G. D. Yancopoulos, M. Karow, and G. Blander, “SIRT4 inhibits glutamate dehydrogenase and opposes the effects of calorie restriction in pancreatic β cells,” Cell, vol. 126, no. 5, pp. 941-954, 2006.
  6. G. Laurent, V. C. de Boer, L. W. Finley, M. Sweeney, H. Lu, T. T. Schug, Y. Cen, S. M. Jeong, X. Li, A. A. Sauve, and M. C. Haigis, “SIRT4 represses peroxisome proliferator-activated receptor alpha activity to suppress hepatic fat oxidation,” Mol Cell Biol, vol. 33, no. 22, pp. 4552-61, Nov, 2013.
  7. B. Liu, W. Che, J. Xue, C. Zheng, K. Tang, J. Zhang, J. Wen, and Y. Xu, “SIRT4 prevents hypoxia-induced apoptosis in H9c2 cardiomyoblast cells,” Cell Physiol Biochem, vol. 32, no. 3, pp. 655-62, 2013.
  8. Y. Li, Y. Zhou, F. Wang, X. Chen, C. Wang, J. Wang, T. Liu, Y. Li, and B. He, “SIRT4 is the last puzzle of mitochondrial sirtuins,” Bioorg Med Chem, vol. 26, no. 14, pp. 3861-3865, Aug 7, 2018.
  9. N. Ahuja, B. Schwer, S. Carobbio, D. Waltregny, B. J. North, V. Castronovo, P. Maechler, and E. Verdin, “Regulation of insulin secretion by SIRT4, a mitochondrial ADP-ribosyltransferase,” J Biol Chem, vol. 282, no. 46, pp. 33583-92, Nov 16, 2007.
  10. E. Michishita, J. Y. Park, J. M. Burneskis, J. C. Barrett, and I. Horikawa, “Evolutionarily conserved and nonconserved cellular localizations and functions of human SIRT proteins,” Mol Biol Cell, vol. 16, no. 10, pp. 4623-35, Oct, 2005.
  11. G. Huang, and G. Zhu, “Sirtuin-4 (SIRT4), a therapeutic target with oncogenic and tumor-suppressive activity in cancer,” OncoTargets and therapy, vol. 11, pp. 3395, 2018.
  12. S. M. Jeong, C. Xiao, L. W. Finley, T. Lahusen, A. L. Souza, K. Pierce, Y.-H. Li, X. Wang, G. Laurent, and N. J. German, “SIRT4 has tumor-suppressive activity and regulates the cellular metabolic response to DNA damage by inhibiting mitochondrial glutamine metabolism,” Cancer cell, vol. 23, no. 4, pp. 450-463, 2013.
  13. R. A. H. van de Ven, D. Santos, and M. C. Haigis, “Mitochondrial Sirtuins and Molecular Mechanisms of Aging,” Trends Mol Med, vol. 23, no. 4, pp. 320-331, Apr, 2017.
  14. L. Wang, H. Zhou, Y. Wang, G. Cui, and L. J. Di, “CtBP maintains cancer cell growth and metabolic homeostasis via regulating SIRT4,” Cell Death Dis, vol. 6, no. 1, pp. e1620, Jan 29, 2015.
  15. D. Komlos, K. D. Mann, Y. Zhuo, C. L. Ricupero, R. P. Hart, A. Y. Liu, and B. L. Firestein, “Glutamate dehydrogenase 1 and SIRT4 regulate glial development,” Glia, vol. 61, no. 3, pp. 394-408, Mar, 2013.
  16. K. A. Hershberger, A. S. Martin, and M. D. Hirschey, “Role of NAD(+) and mitochondrial sirtuins in cardiac and renal diseases,” Nat Rev Nephrol, vol. 13, no. 4, pp. 213-225, Apr, 2017.
  17. S. Shukla, A. Sharma, V. K. Pandey, S. Raisuddin, and P. Kakkar, “Concurrent acetylation of FoxO1/3a and p53 due to sirtuins inhibition elicit Bim/PUMA mediated mitochondrial dysfunction and apoptosis in berberine-treated HepG2 cells,” Toxicol Appl Pharmacol, vol. 291, pp. 70-83, Jan 15, 2016.
  18. P. J. Fernandez-Marcos, and M. Serrano, “Sirt4: the glutamine gatekeeper,” Cancer Cell, vol. 23, no. 4, pp. 427-8, Apr 15, 2013.
  19. D. Germain, “Sirtuins and the Estrogen Receptor as Regulators of the Mammalian Mitochondrial UPR in Cancer and Aging,” Adv Cancer Res, vol. 130, pp. 211-56, 2016.
  20. M. Miyo, H. Yamamoto, M. Konno, H. Colvin, N. Nishida, J. Koseki, K. Kawamoto, H. Ogawa, A. Hamabe, and M. Uemura, “Tumour-suppressive function of SIRT4 in human colorectal cancer,” British journal of cancer, vol. 113, no. 3, pp. 492, 2015.
  21. A. Csibi, S. M. Fendt, C. Li, G. Poulogiannis, A. Y. Choo, D. J. Chapski, S. M. Jeong, J. M. Dempsey, A. Parkhitko, T. Morrison, E. P. Henske, M. C. Haigis, L. C. Cantley, G. Stephanopoulos, J. Yu, and J. Blenis, “The mTORC1 pathway stimulates glutamine metabolism and cell proliferation by repressing SIRT4,” Cell, vol. 153, no. 4, pp. 840-54, May 9, 2013.
  22. G. Huang, F. Cui, F. Yu, H. Lu, M. Zhang, H. Tang, and Z. Peng, “Sirtuin-4 (SIRT4) is downregulated and associated with some clinicopathological features in gastric adenocarcinoma,” Biomedicine & Pharmacotherapy, vol. 72, pp. 135-139, 2015.
  23. M. M. Bradford, “A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding,” Analytical biochemistry, vol. 72, no. 1-2, pp. 248-254, 1976.
  24. M. Miyo, H. Yamamoto, M. Konno, H. Colvin, N. Nishida, J. Koseki, K. Kawamoto, H. Ogawa, A. Hamabe, M. Uemura, J. Nishimura, T. Hata, I. Takemasa, T. Mizushima, Y. Doki, M. Mori, and H. Ishii, “Tumour-suppressive function of SIRT4 in human colorectal cancer,” Br J Cancer, vol. 113, no. 3, pp. 492-9, Jul 28, 2015.
  25. H. Sun, D. Huang, G. Liu, F. Jian, J. Zhu, and L. Zhang, “SIRT4 acts as a tumor suppressor in gastric cancer by inhibiting cell proliferation, migration, and invasion,” Onco Targets Ther, vol. 11, pp. 3959-3968, 2018.
  26. A. Csibi, S.-M. Fendt, C. Li, G. Poulogiannis, A. Y. Choo, D. J. Chapski, S. M. Jeong, J. M. Dempsey, A. Parkhitko, and T. Morrison, “The mTORC1 pathway stimulates glutamine metabolism and cell proliferation by repressing SIRT4,” Cell, vol. 153, no. 4, pp. 840-854, 2013.

Downloads

Published

2020-06-30

Issue

Section

Research Articles

How to Cite

[1]
Abdul-Nazif Mahmud, Feilun Cui, Xue Bo, Jianpeng Hu, Tingjun Liu, Muslimat Kehinde Adebis, Said Abdulrahman Salim, Aaron Gia Kanton, " SIRT4 Overexpression Promotes the Inhibition of Cell Proliferation and Invasion in Prostate Cancer, International Journal of Scientific Research in Science and Technology(IJSRST), Online ISSN : 2395-602X, Print ISSN : 2395-6011, Volume 7, Issue 3, pp.276-284, May-June-2020. Available at doi : https://doi.org/10.32628/IJSRST207347