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Selenoprotein Genes Exhibit Differential Expression Patterns Between Hepatoma HepG2 and Normal Hepatocytes LO2 Cell Lines

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Abstract

The purpose of this study was to compare messenger RNA (mRNA) expression of selenoprotein genes between hepatoma HepG2 and normal hepatocytes LO2 cell lines. Liver HepG2 and LO2 cells were cultured in 12-well plates under the same condition until cells grew to complete confluence, and then cells were harvested for total RNA and protein extraction. The qPCRs were performed to compare gene expression of 14 selenoprotein genes and 5 cancer signaling-related genes. Enzyme activities were also assayed. The results showed that human hepatoma HepG2 cells grew faster than normal hepatocytes LO2 cells. Among the genes investigated, 10 selenoprotein genes (Gpx1, Gpx3, Gpx4, Selx, Sepp, Sepw1, Sepn1, Selt, Seli, Selh) and 3 cancer signaling-related genes (Bcl-2A, caspase-3, and P38) were upregulated (P < 0.05), while Selo and Bcl-2B were downregulated (P < 0.05) in hepatoma HepG2 cells compared to LO2 cells. Significant correlations were found between selenoprotein genes and the cancer signaling-related genes Caspase3, P53, Bc1-2A, and Bc1-2B. Our results revealed that selenoprotein genes were aberrantly expressed in hepatoma HepG2 cells compared to normal liver LO2 cells, which indicated that those selenoprotein genes may play important roles in the occurrence and development of liver carcinogenesis.

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References

  1. Siegel R, DeSantis C, Virgo K, Stein K, Mariotto A, Smith T, Cooper D, Gansler T, Lerro C, Fedewa S (2012) Cancer treatment and survivorship statistics. CA Cancer J Clin 62:220–241

    Article  PubMed  Google Scholar 

  2. Whanger PD (2004) Selenium and its relationship to cancer: an update dagger. Br J Nutr 91:11–18

    Article  CAS  PubMed  Google Scholar 

  3. Clark LC, Combs GF, Turnbull BW, Slate EH, Chalker DK, Chow J, Davis LS, Glover RA, Graham GF, Gross EG (1996) Effects of seleniumsupplementation for cancer prevention in patients with carcinoma of the skin. A randomized controlled trial. JAMA 276:1957–1963

    Article  CAS  PubMed  Google Scholar 

  4. Duffield-Lillico AJ, Dalkin BL, Reid ME, Turnbull BW, Slate EH, Jacobs ET, Marshall JR, Clark LC (2003) Selenium supplementation, baseline plasma selenium status and incidence of prostate cancer: an analysis of the complete treatment period of the Nutritional Prevention of Cancer Trial. BJU Int 91:608–612

    Article  CAS  PubMed  Google Scholar 

  5. Irons R, Carlson BA, Hatfield DL, Davis CD (2006) Both selenoproteins and low molecular weight selenocompounds reduce colon cancer risk in mice with genetically impaired selenoprotein expression. J Nutr 136:1311–1317

    CAS  PubMed  Google Scholar 

  6. Clark LC, Dalkin B, Krongrad A, Combs GF Jr, Turnbul BW, Slate EH, Witherington R, Herlong JH, Janosko E, Carpenter D (1998) Decreased incidence of prostate cancer with selenium supplementation: results of a double-blind cancer prevention trial. Br J Urol 81:730–734

    Article  CAS  PubMed  Google Scholar 

  7. Ip C (1998) Lessons from basic research in selenium and cancer prevention. J Nutr 128:1845–1854

    CAS  PubMed  Google Scholar 

  8. Lobanov AV, Hatfield DL, Gladyshev VN (2009) Eukaryotic selenoproteins and selenoproteomes. Biochim Biophys Acta 1790:1424–1428

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  9. Zhuo P, Diamond AM (2009) Molecular mechanisms by which selenoproteins affect cancer risk and progression. Biochim Biophys Acta 1790:1546–1554

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  10. Meplan C, Rohrmann S, Steinbrecher A, Schomburg L, Jansen E, Linseisen J, Hesketh J (2012) Polymorphisms in thioredoxin reductase and selenoprotein K genes and selenium status modulate risk of prostate cancer. PLoS ONE 7(11):e48709

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  11. Liu J, Hinkhouse MM, Sun W, Weydert CJ, Ritchie JM, Oberley LW, Cullen JJ (2004) Redox regulation of pancreatic cancer cell growth: role of glutathione peroxidase in the suppression of the malignant phenotype. Hum Gene Ther 15:239–250

    Article  CAS  PubMed  Google Scholar 

  12. Heirman I, Ginneberge D, Brigelius-Floh´e R, Hendrickx N, Agostinis P, Brouckaert P, Rottiers P, Grooten J (2006) Blocking tumor cell eicosanoid synthesis by GPx 4 impedes tumor growth and malignancy. Free Radic Biol Med 40:285–294

    Article  CAS  PubMed  Google Scholar 

  13. Novoselov SV, Calvisi DF, Labunskyy VM, Factor VM, Carlson BA, Fomenko DE, Moustafa ME, Hatfield DL, Gladyshev VN (2005) Selenoprotein deficiency and high levels of selenium compounds can effectively Selenium-biofortified porcine serum on cancer cells inhibit hepatocarcinogenesis in transgenic mice. Oncogene 24:8003–8011

    Article  CAS  PubMed  Google Scholar 

  14. Castello G, Scala S, Palmieri G, Curley SA, Izzo F (2010) HCV-Related hepatocellular carcinoma: from chronic inflammation to cancer. Clin Immunol 134:237–250

    Article  CAS  PubMed  Google Scholar 

  15. Kryukov GV, Castellano S, Novoselov SV, Lobanov AV, Zehtab O, Guigo R, Gladyshev VN (2003) Characterization of mammalian selenoproteomes. Science 300:1439–1443

    Article  CAS  PubMed  Google Scholar 

  16. Mosmann T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J lmmunol Methods 65:55–63

    Article  CAS  Google Scholar 

  17. Liu Y, Zhao H, Zhang QS, Tang JY, Li K, Xia XJ, Wang KN, Li K, Lei XG (2012) Prolonged dietary selenium deficiency or excess does not globally affect selenoprotein gene expression and/or protein production in various tissues of pigs. J Nutr 142(8):1410–1416

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  18. Zhou JC, Zhao H, Li JG, Xia XJ, Wang KN, ZhangYJ LY, Zhao Y, Lei XG (2009) Selenoprotein gene expression in thyroid and pituitary of young pigs is not affected by dietary selenium deficiency or excess. J Nutr 139:1061–1066

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. Haupt Y, Maya R, Kazaz A, Oren M (1997) Mdm2 promotes the rapid degradation of p53. Nature 387:296–299

    Article  CAS  PubMed  Google Scholar 

  20. Hockenbery D, Nu ez G, Milliman C, Schreiber R, Korsmeyer S (1990) Bcl-2 is an inner mitochondrial membrane protein that blocks programmed cell death. Nature 348:334–336

    Article  CAS  PubMed  Google Scholar 

  21. Otake Y, Soundararajan S, Sengupta TK, Kio EA, Smith JC, Roman MP (2007) Overexpression of nucleolin in chronic lymphocytic leukemia cells induces stabilization of bcl-2 mRNA. Blood 109(7):3069–3075

    PubMed Central  CAS  PubMed  Google Scholar 

  22. Hwang DY, Cho JS, Oh JH, Shim SB, Jee SW, Lee SH, Seo SJ, Lee SK, Lee SH, Kim YK (2005) Differentially expressed genes in transgenic mice carrying human mutant presenilin-2 (N141I): correlation of selenoprotein M with Alzheimer's disease. Neurochem Res 30(8):1009–1019

    Article  CAS  PubMed  Google Scholar 

  23. Rebsch CM, Penna FJ, Copeland PR (2006) Selenoprotein expression is regulated at multiple levels in prostate cells. Cell Res 16(12):940–948

    Article  CAS  PubMed  Google Scholar 

  24. Rayman MP (2005) Selenium in cancer prevention: a review of the evidence and mechanism of action. Proc Nutr Soc 64(4):527–542

    Article  CAS  PubMed  Google Scholar 

  25. Nasr MA, Fedele MJ, Esser K, Diamond AM (2004) GPx-1 modulates Akt and P70S6K phosphorylation and Gadd45 levels in MCF-7 cells. Free Radic Biol Med 37:187–195

    Article  CAS  PubMed  Google Scholar 

  26. Gonzalez-Moreno O, Boque N, Redrado M, Milagro F, Campion J, Endermann T, Takahashi K, Saito Y, Catena R, Schomburg L (2011) Selenoprotein-P is down-regulated in prostate cancer, which results in lack of protection against oxidative damage. Prostate 71:824–834

    Article  CAS  PubMed  Google Scholar 

  27. Shibata T, Arisawa T, Tahara T, Ohkubo M, Yoshioka D, Maruyama N, Fujita H, Kamiya Y, Nakamura M, Nagasaka M (2009) SEPS1 gene-105G > A promoter polymorphism influences the susceptibility to gastric cancer in the Japanese population. BMC Gastroenterol 9:2

    Article  PubMed Central  PubMed  Google Scholar 

  28. Zhuo P, Diamond AM (2009) An analysis of molecular mechanisms by which selenoproteins affect cancer risk and progression. Cancer prevention by selenium. Biochim Biophys Acta 1790:1546–1554

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  29. Davis CD, Tsuji PA, Milner JA (2012) Selenoproteins and cancer prevention. Annu Rev Nutr 32:73–95

    Article  CAS  PubMed  Google Scholar 

  30. Huang C, Ding G, Gu C, Zhou J, Kuang M, Ji Y, He Y, Kondo T, Fan J (2012) Decreased selenium-binding protein 1 enhances glutathione peroxidase 1 activity and down-regulates HIF-1alpha to promote hepatocellular carcinoma invasiveness. Clin Cancer Res 18:3042–3053

    Article  CAS  PubMed  Google Scholar 

  31. Guariniello S, Colonna G, Raucci R, Costantini M, Bernardo GD, Bergantino F, Castello G, Costantini S (2014) Structure-function relationship and evolutionary history of the human selenopreotein M (SelM) found over-expressed in hepatocellular carcinoma. Biochim Biophys Acta 1844:447–456

    Article  CAS  PubMed  Google Scholar 

  32. Sun LH, Li JG, Zhao H, Shi J, Huang JQ, Wang KN, Xia XJ, Li L, Lei XG (2013) Porcine serum can be biofortified with selenium to inhibit proliferation of three types of human cancer cells. J Nutr 143:1115–1122

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  33. Valko M, Rhodes CJ, Moncol J, Izakovis M, Mazur M (2007) Free radicals, metals and antioxidant in oxidative stress-induced cancer. Chem Biol Interact 160:1–40

    Article  Google Scholar 

Download references

Acknowledgments

This work was supported partly by the National Natural Science Foundation of China (No. 31272468 and 31072043) and by the Special Research Funding for Discipline Construction in Sichuan Agricultural University (to H. Zhao).

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Correspondence to Hua Zhao.

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Jiayong Tang is a co-first author.

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Zhao, H., Tang, J., Xu, J. et al. Selenoprotein Genes Exhibit Differential Expression Patterns Between Hepatoma HepG2 and Normal Hepatocytes LO2 Cell Lines. Biol Trace Elem Res 167, 236–241 (2015). https://doi.org/10.1007/s12011-015-0323-6

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  • DOI: https://doi.org/10.1007/s12011-015-0323-6

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