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Expression profiles of human endogenous retrovirus (HERV)-K and HERV-R Env proteins in various cancers

  • Ko, Eun-Ji (Department of Parasitology and Genetics, Kosin University College of Medicine) ;
  • Song, Kyoung Seob (Department of Physiology, Kosin University College of Medicine) ;
  • Ock, Mee Sun (Department of Parasitology and Genetics, Kosin University College of Medicine) ;
  • Choi, Yung Hyun (Department of Biochemistry, College of Oriental Medicine, Dongeui University) ;
  • Kim, Suhkmann (Department of Chemistry, College of Natural Sciences, Pusan National University) ;
  • Kim, Heui-Soo (Department of Biological Sciences, College of Natural Sciences, Pusan National University) ;
  • Cha, Hee-Jae (Department of Parasitology and Genetics, Kosin University College of Medicine)
  • Received : 2020.11.10
  • Accepted : 2021.02.21
  • Published : 2021.07.31

Abstract

The vertebrate genome contains an endogenous retrovirus that has been inherited from the past millions of years. Although approximately 8% of human chromosomal DNA consists of sequences derived from human endogenous retrovirus (HERV) fragments, most of the HERVs are currently inactive and noninfectious due to recombination, deletions, and mutations after insertion into the host genome. Several studies suggested that Human endogenous retroviruses (HERVs) factors are significantly related to certain cancers. However, only limited studies have been conducted to analyze the expression of HERV derived elements at protein levels in certain cancers. Herein, we analyzed the expression profiles of HERV-K envelope (Env) and HERV-R Env proteins in eleven different kinds of cancer tissues. Furthermore, the expression patterns of both protein and correlation with various clinical data in each tissue were analyzed. The expressions of both HERV-K Env and HERV-R Env protein were identified to be significantly high in most of the tumors compared with normal surrounding tissues. Correlations between HERV Env expressions and clinical investigations varied depending on the HERV types and cancers. Overall expression patterns of HERV-K Env and HERV-R Env proteins were different in every individual but a similar pattern of expressions was observed in the same individual. These results demonstrate the expression profiles of HERV-K and HERV-R Env proteins in various cancer tissues and provide a good reference for the association of endogenous retroviral Env proteins in the progression of various cancers. Furthermore, the results elucidate the relationship between HERV-Env expression and the clinical significance of certain cancers.

Keywords

Acknowledgement

This work was supported by the National Research Foundation Grant funded by the Korean Government (NRF-2016R1D1A3B01007444).

References

  1. Contreras-Galindo R, Kaplan MH, Leissner P et al (2008) Human endogenous retrovirus K (HML-2) elements in the plasma of people with lymphoma and breast cancer. J Virol 82, 9329-9336 https://doi.org/10.1128/JVI.00646-08
  2. Conley AB, Piriyapongsa J and Jordan IK (2008) Retroviral promoters in the human genome. Bioinformatics 24, 1563-1567 https://doi.org/10.1093/bioinformatics/btn243
  3. Oja M, Peltonen J, Blomberg J and Kaski S (2007) Methods for estimating human endogenous retrovirus activities from EST databases. BMC Bioinformatics 8 Suppl 2, S11
  4. Perot P, Mugnier N, Montgiraud C et al (2012) Microarray-based sketches of the HERV transcriptome landscape. PLoS One 7, e40194 https://doi.org/10.1371/journal.pone.0040194
  5. Ishida T, Obata Y, Ohara N et al (2008) Identification of the HERV-K gag antigen in prostate cancer by SEREX using autologous patient serum and its immunogenicity. Cancer Immun 8, 15
  6. Hahn S, Ugurel S, Hanschmann KM et al (2008) Serological response to human endogenous retrovirus K in melanoma patients correlates with survival probability. AIDS Res Hum Retroviruses 24, 717-723 https://doi.org/10.1089/aid.2007.0286
  7. Li M, Radvanyi L, Yin B et al (2017) Downregulation of Human endogenous retrovirus type K (HERV-K) viral env RNA in pancreatic cancer cells decreases cell proliferation and tumor growth. Clin Cancer Res 23, 5892-5911 https://doi.org/10.1158/1078-0432.CCR-17-0001
  8. Wang-Johanning F, Rycaj K, Plummer JB et al (2012) Immunotherapeutic potential of anti-human endogenous retrovirus-K envelope protein antibodies in targeting breast tumors. J Natl Cancer Inst 104, 189-210 https://doi.org/10.1093/jnci/djr540
  9. Kewitz S and Staege MS (2013) Expression and regulation of the endogenous retrovirus 3 in Hodgkin's lymphoma cells. Front Oncol 3, 179 https://doi.org/10.3389/fonc.2013.00179
  10. Lee SH, Kang YJ, Jo JO et al (2014) Elevation of human ERV3-1 env protein expression in colorectal cancer. J Clin Pathol 67, 840-844 https://doi.org/10.1136/jclinpath-2013-202089
  11. Rhyu DW, Kang YJ, Ock MS et al (2014) Expression of human endogenous retrovirus env genes in the blood of breast cancer patients. Int J Mol Sci 15, 9173-9183 https://doi.org/10.3390/ijms15069173
  12. Jo JO, Kang YJ, Ock MS et al (2016) Expression profiles of HERV-K Env protein in normal and cancerous tissues. Genes Genom 38, 91-107 https://doi.org/10.1007/s13258-015-0343-9
  13. Yun KY, Ko EJ, Kim HY et al (2017) Long interspersed element-1 open reading frame 1 protein expression profiles in ovarian cancers. Genes Genom 39, 1157-1162 https://doi.org/10.1007/s13258-017-0589-5
  14. Zhao J, Rycaj K, Geng S et al (2011) Expression of human endogenous retrovirus type K envelope protein is a novel candidate prognostic marker for human breast cancer. Genes Cancer 2, 914-922 https://doi.org/10.1177/1947601911431841
  15. Krone B and Grange JM (2010) Melanoma, Darwinian medicine and the inner world. J Cancer Res Clin Oncol 136, 1787-1794 https://doi.org/10.1007/s00432-010-0949-x
  16. Buscher K, Trefzer U, Hofmann M, Sterry W, Kurth R and Denner J (2005) Expression of human endogenous retrovirus K in melanomas and melanoma cell lines. Cancer Res 65, 4172-4180 https://doi.org/10.1158/0008-5472.CAN-04-2983
  17. Kang YJ, Jo JO, Ock MS et al (2014) Human ERV3-1 env protein expression in various human tissues and tumours. J Clin Pathol 67, 86-90 https://doi.org/10.1136/jclinpath-2013-201841
  18. Kurth R and Bannert N (2010) Beneficial and detrimental effects of human endogenous retroviruses. Int J Cancer 126, 306-314 https://doi.org/10.1002/ijc.24902
  19. Bannert N and Kurth R (2004) Retroelements and the human genome: new perspectives on an old relation. Proc Natl Acad Sci U S A 101 Suppl 2, 14572-14579 https://doi.org/10.1073/pnas.0404838101
  20. Romanish MT, Cohen CJ and Mager DL (2010) Potential mechanisms of endogenous retroviral-mediated genomic instability in human cancer. Semin Cancer Biol 20, 246-253 https://doi.org/10.1016/j.semcancer.2010.05.005
  21. Freimanis G, Hooley P, Ejtehadi HD et al (2010) A role for human endogenous retrovirus-K (HML-2) in rheumatoid arthritis: investigating mechanisms of pathogenesis. Clin Exp Immunol 160, 340-347 https://doi.org/10.1111/j.1365-2249.2010.04110.x
  22. Jeong BH, Lee YJ, Carp RI and Kim YS (2010) The prevalence of human endogenous retroviruses in cerebrospinal fluids from patients with sporadic Creutzfeldt-Jakob disease. J Clin Virol 47, 136-142 https://doi.org/10.1016/j.jcv.2009.11.016
  23. Blond JL, Lavillette D, Cheynet V et al (2000) An envelope glycoprotein of the human endogenous retrovirus HERV-W is expressed in the human placenta and fuses cells expressing the type D mammalian retrovirus receptor. J Virol 74, 3321-3329 https://doi.org/10.1128/JVI.74.7.3321-3329.2000
  24. Mi S, Lee X, Li X et al (2000) Syncytin is a captive retroviral envelope protein involved in human placental morphogenesis. Nature 403, 785-789 https://doi.org/10.1038/35001608
  25. Tugnet N, Rylance P, Roden D, Trela M and Nelson P (2013) Human endogenous retroviruses (HERVs) and autoimmune rheumatic disease: is there a link? Open Rheumatol J 7, 13-21 https://doi.org/10.2174/1874312901307010013
  26. Lindeskog M and Blomberg J (1997) Spliced human endogenous retroviral HERV-H env transcripts in T-cell leukaemia cell lines and normal leukocytes: alternative splicing pattern of HERV-H transcripts. J Gen Virol 78 (Pt 10), 2575-2585 https://doi.org/10.1099/0022-1317-78-10-2575
  27. Wang-Johanning F, Frost AR, Jian B et al (2003) Detecting the expression of human endogenous retrovirus E envelope transcripts in human prostate adenocarcinoma. Cancer 98, 187-197 https://doi.org/10.1002/cncr.11451
  28. Kaufmann S, Sauter M, Schmitt M et al (2010) Human endogenous retrovirus protein Rec interacts with the testicular zinc-finger protein and androgen receptor. J Gen Virol 91, 1494-1502 https://doi.org/10.1099/vir.0.014241-0
  29. Cegolon L, Salata C, Weiderpass E, Vineis P, Palu G and Mastrangelo G (2013) Human endogenous retroviruses and cancer prevention: evidence and prospects. BMC Cancer 13, 4 https://doi.org/10.1186/1471-2407-13-4
  30. Reiche J, Pauli G and Ellerbrok H (2010) Differential expression of human endogenous retrovirus K transcripts in primary human melanocytes and melanoma cell lines after UV irradiation. Melanoma Res 20, 435-440 https://doi.org/10.1097/CMR.0b013e32833c1b5d
  31. Serafino A, Balestrieri E, Pierimarchi P et al (2009) The activation of human endogenous retrovirus K (HERV-K) is implicated in melanoma cell malignant transformation. Exp Cell Res 315, 849-862 https://doi.org/10.1016/j.yexcr.2008.12.023
  32. Wang-Johanning F, Frost AR, Jian B, Epp L, Lu DW and Johanning GL (2003) Quantitation of HERV-K env gene expression and splicing in human breast cancer. Oncogene 22, 1528-1535 https://doi.org/10.1038/sj.onc.1206241