Skip to main content

Advertisement

Log in

MicroRNA Expression Profiles in Kaposi’s Sarcoma

  • Research
  • Published:
Pathology & Oncology Research

Abstract

Kaposi’s sarcoma (KS) is a mesenchymal tumor, caused by Human herpesvirus 8 (HHV8) with molecular and cytogenetic changes poorly understood. To gain further insight on the underlying molecular changes in KS, we performed microRNA (miRNA) microarray analysis of 17 Kaposi’s sarcoma specimens. Three normal skin specimens were used as controls. The most significant differentially expressed miRNA were confirmed by quantitative reverse transcriptase polymerase chain reaction (RT-PCR). We detected in KS versus normal skin 185 differentially expressed miRNAs, 76 were upregulated and 109 were downregulated. The most significantly downregulated miRNAs were miR-99a, miR-200 family, miR-199b-5p, miR-100 and miR-335, whereas kshv-miR-K12-4-3p, kshv-miR-K12-1, kshv-miR-K12-2, kshv-miR-K12-4-5p and kshv-miR-K12-8 were significantly upregulated. High expression levels of kshv-miR-K12-1 (p = 0.004) and kshv-miR-K12-4-3p (p = 0.001) was confirmed by RT-PCR. The predicted target genes for differentially expressed miRNAs included genes which are involved in a variety of cellular processes such as angiogenesis (i.e. THBS1) and apoptosis (i.e. CASP3, MCL1), suggesting a role for these miRNAs in Kaposi’s sarcoma pathogenesis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Foreman KE (2001) Kaposis sarcoma: the role of HHV-8 and HIV-1 in pathogenesis. Expert Rev Mol Med 2001:1–17

    PubMed  Google Scholar 

  2. Feller L, Lemmer J, Wood NH et al (2007) HIV-associated oral kaposi sarcoma and HHV-8: a review. J Int Acad Periodontol 9:129–136

    PubMed  Google Scholar 

  3. Ambros V (2003) MicroRNA pathways in flies and worms: growth, death, fat, stress, and timing. Cell 113:673–676

    Article  CAS  PubMed  Google Scholar 

  4. Antman K, Chang Y (2000) Kaposi’s sarcoma. N Engl J Med 342:1027–1038

    Article  CAS  PubMed  Google Scholar 

  5. Kiuru-Kuhlefelt S, Sarlomo-Rikala M, Larramendy ML et al (2000) FGF4 and INT2 oncogenes are amplified and expressed in kaposi’s sarcoma. Mod Pathol 13:433–437

    Article  CAS  PubMed  Google Scholar 

  6. Sun R, Lin SF, Staskus K et al (1999) Kinetics of kaposi’s sarcoma-associated herpesvirus gene expression. J Virol 73:2232–2242

    CAS  PubMed Central  PubMed  Google Scholar 

  7. Raggo C, Ruhl R, McAllister S et al (2005) Novel cellular genes essential for transformation of endothelial cells by kaposi’s sarcoma-associated herpesvirus. Cancer Res 65:5084–5095

    Article  CAS  PubMed  Google Scholar 

  8. Samols MA, Skalsky RL, Maldonado AM et al (2007) Identification of cellular genes targeted by KSHV-encoded microRNAs. PLoS Pathog 3:e65

    Article  PubMed Central  PubMed  Google Scholar 

  9. Croce CM (2009) Causes and consequences of microRNA dysregulation in cancer. Nat Rev Genet 10:704–714

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. Sassen S, Miska EA, Caldas C (2008) MicroRNA: implications for cancer. Virchows Arch 452:1–10

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  11. Volinia S, Calin GA, Liu CG et al (2006) A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci U S A 103:2257–2261

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Lu J, Getz G, Miska EA et al (2005) MicroRNA expression profiles classify human cancers. Nature 435:834–838

    Article  CAS  PubMed  Google Scholar 

  13. Borze I, Guled M, Musse S et al (2010) MicroRNA microarrays on archive bone marrow core biopsies of leukemias-method validation. Leuk Res 35:188–195

    Article  PubMed  Google Scholar 

  14. Zhang X, Chen J, Radcliffe T et al (2008) An array-based analysis of microRNA expression comparing matched frozen and formalin-fixed paraffin-embedded human tissue samples. J Mol Diagn 10:513–519

    Article  PubMed Central  PubMed  Google Scholar 

  15. Mosakhani N, Sarhadi VK, Borze I et al (2012) MicroRNA profiling differentiates colorectal cancer according to KRAS status. Genes Chromosom Cancer 51:1–9

    Article  CAS  PubMed  Google Scholar 

  16. Schmittgen TD, Livak KJ (2008) Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc 3:1101–1108

    Article  CAS  PubMed  Google Scholar 

  17. Griffiths-Jones S, Saini HK, van Dongen S et al (2008) miRBase: tools for microRNA genomics. Nucleic Acids Res 36:D154–D158

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  18. Lewis BP, Burge CB, Bartel DP (2005) Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 120:15–20

    Article  CAS  PubMed  Google Scholar 

  19. Betel D, Wilson M, Gabow A et al (2008) The microRNA.org resource: targets and expression. Nucleic Acids Res 36:D149–D153

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  20. Wang X, El Naqa IM (2008) Prediction of both conserved and nonconserved microRNA targets in animals. Bioinformatics 24:325–332

    Article  PubMed  Google Scholar 

  21. Wang X (2008) miRDB: a microRNA target prediction and functional annotation database with a wiki interface. RNA 14:1012–1017

    Article  CAS  PubMed  Google Scholar 

  22. Nuovo GJ, Wu X, Volinia S et al (2010) Strong inverse correlation between microRNA-125b and human papillomavirus DNA in productive infection. Diagn Mol Pathol 19:135–143

    Article  CAS  PubMed  Google Scholar 

  23. Schickel R, Boyerinas B, Park SM et al (2008) MicroRNAs: key players in the immune system, differentiation, tumorigenesis and cell death. Oncogene 27:5959–5974

    Article  CAS  PubMed  Google Scholar 

  24. Merimsky O, Jiveliouk I, Sagi-Eisenberg R (2008) Targeting mTOR in HIV-negative classic kaposi’s sarcoma. Sarcoma 2008:825093

    Article  PubMed Central  PubMed  Google Scholar 

  25. Gregory PA, Bert AG, Paterson EL et al (2008) The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1. Nat Cell Biol 10:593–601

    Article  CAS  PubMed  Google Scholar 

  26. Karasek M (2007) Differentiation of postembryonic skin endothelial cells. J Investig Dermatol 127:2710–2712

    Article  CAS  PubMed  Google Scholar 

  27. Park SM, Gaur AB, Lengyel E et al (2009) The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2. Genes Dev 22:894–907

    Article  Google Scholar 

  28. O’Hara AJ, Wang L, Dezube BJ et al (2009) Tumor suppressor microRNAs are underrepresented in primary effusion lymphoma and kaposi sarcoma. Blood 113:5938–5941

    Article  PubMed  Google Scholar 

  29. Park SM, Shell S, Radjabi AR et al (2007) Let-7 prevents early cancer progression by suppressing expression of the embryonic gene HMGA2. Cell Cycle 6:2585–2590

    Article  CAS  PubMed  Google Scholar 

  30. Johnson SM, Grosshans H, Shingara J et al (2005) RAS is regulated by the let-7 microRNA family. Cell 120:635–647

    Article  CAS  PubMed  Google Scholar 

  31. Zhang B, Pan X, Cobb GP et al (2007) microRNAs as oncogenes and tumor suppressors. Dev Biol 302:1–12

    Article  CAS  PubMed  Google Scholar 

  32. Moustakas A, Pardali K, Gaal A et al (2002) Mechanisms of TGF-beta signaling in regulation of cell growth and differentiation. Immunol Lett 82:85–91

    Article  CAS  PubMed  Google Scholar 

  33. Di Bartolo DL, Cannon M, Liu YF et al (2008) KSHV LANA inhibits TGF-beta signaling through epigenetic silencing of the TGF-beta type II receptor. Blood 111:4731–4740

    Article  PubMed  Google Scholar 

  34. Seo T, Park J, Choe J (2005) Kaposi’s sarcoma-associated herpesvirus viral IFN regulatory factor 1 inhibits transforming growth factor-beta signaling. Cancer Res 65:1738–1747

    Article  CAS  PubMed  Google Scholar 

  35. Tomita M, Choe J, Tsukazaki T et al (2004) The kaposi’s sarcoma-associated herpesvirus K-bZIP protein represses transforming growth factor beta signaling through interaction with CREB-binding protein. Oncogene 23:8272–8281

    Article  CAS  PubMed  Google Scholar 

  36. Meng F, Henson R, Wehbe-Janek H et al (2007) MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer. Gastroenterology 133:647–658

    Article  CAS  PubMed  Google Scholar 

  37. Zhu S, Si ML, Wu H et al (2007) MicroRNA-21 targets the tumor suppressor gene tropomyosin 1 (TPM1). J Biol Chem 282:14328–14336

    Article  CAS  PubMed  Google Scholar 

  38. Moore PS, Chang Y (2001) Molecular virology of kaposi’s sarcoma-associated herpesvirus. Philos Trans R Soc Lond B Biol Sci 356:499–516

    Article  CAS  PubMed  Google Scholar 

  39. Mott JL, Kobayashi S, Bronk SF et al (2007) Mir-29 regulates mcl-1 protein expression and apoptosis. Oncogene 26:6133–6140

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  40. Marshall V, Martro E, Labo N et al (2010) Kaposi sarcoma (KS)-associated herpesvirus microRNA sequence analysis and KS risk in a european AIDS-KS case control study. J Infect Dis 202:1126–1135

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  41. Hansen A, Henderson S, Lagos D et al (2010) KSHV-encoded miRNAs target MAF to induce endothelial cell reprogramming. Genes Dev 24:195–205

    Article  CAS  PubMed  Google Scholar 

  42. Cai X, Lu S, Zhang Z et al (2005) Kaposi’s sarcoma-associated herpesvirus expresses an array of viral microRNAs in latently infected cells. Proc Natl Acad Sci U S A 102:5570–5575

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  43. Qin Z, Kearney P, Plaisance K et al (2010) Pivotal advance: Kaposi’s sarcoma-associated herpesvirus (KSHV)-encoded microRNA specifically induce IL-6 and IL-10 secretion by macrophages and monocytes. J Leukoc Biol 87:25–34

    Article  CAS  PubMed  Google Scholar 

  44. Bellare P, Ganem D (2009) Regulation of KSHV lytic switch protein expression by a virus-encoded microRNA: an evolutionary adaptation that fine-tunes lytic reactivation. Cell Host Microbe 6:570–575

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  45. Suffert G, Malterer G, Hausser J et al (2011) Kaposi’s sarcoma herpesvirus microRNAs target caspase 3 and regulate apoptosis. PLoS Pathog 7:e1002405

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  46. Abend JR, Uldrick T, Ziegelbauer JM (2010) Regulation of tumor necrosis factor-like weak inducer of apoptosis receptor protein (TWEAKR) expression by kaposi’s sarcoma-associated herpesvirus microRNA prevents TWEAK-induced apoptosis and inflammatory cytokine expression. J Virol 84:12139–121351

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  47. Ziegelbauer JM, Sullivan CS, Ganem D (2009) Tandem array-based expression screens identify host mRNA targets of virus-encoded microRNAs. Nat Genet 41:130–134

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  48. Calin GA, Sevignani C, Dumitru CD et al (2004) Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci U S A 101:2999–3004

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  49. Pyakurel P, Montag U, Castanos-Velez E et al (2006) CGH of microdissected kaposi’s sarcoma lesions reveals recurrent loss of chromosome Y in early and additional chromosomal changes in late tumour stages. AIDS 20:1805–1812

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We thank Neda Mosakhani, M.D. for the guidance and help in performing in PCR. This project was supported by prof. Sakari Knuutila’s grant from the special state subsidy research funds appropriated to the Helsinki and Uusimaa Hospital District (HUS EVO) and the TEKES (the Finnish Funding Agency for Technology and Innovation) Multibio project (grant no. 40141/07), Finland, as well as by the TD Project Code 222 (CNCSIS), Romania.

Disclosure/Conflict of Interest

The authors declare no conflict of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Sakari Knuutila.

Additional information

Ana Maria Catrina (Ene) and Ioana Borze equally contributed to this study.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Catrina (Ene), A.M., Borze, I., Guled, M. et al. MicroRNA Expression Profiles in Kaposi’s Sarcoma. Pathol. Oncol. Res. 20, 153–159 (2014). https://doi.org/10.1007/s12253-013-9678-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12253-013-9678-1

Keywords

Navigation