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The microRNA-29 plays a central role in osteosarcoma pathogenesis and progression

  • Molecular Biology of the Cell
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Abstract

Osteosarcoma is the most common type of bone cancer, with a peak incidence in the early childhood. The relationship between microRNAs (miRNAs) and cancer development attracted more and more attention over the last few years. Members of the miRNA-29 family, including miRNA-29a, miRNA-29b, and miRNA-29c were shown to participate in the development of rhabdomyosarcoma and hepatocarcinogenesis. Here, it has been demonstrated miRNA-29a and miRNA-29b expression levels to be downregulated in most of the osteosarcoma tissues (23 from 30). Besides, miRNA-29a displayed ability to induce apoptosis in both U2OS and SAOS-2 osteoblastic cells. While miRNA-29 members induced apoptosis through p53 gene activation, the effect of miRNA-29a on osteoblastic cells was independent on p53 expression level. Moreover, Bcl-2 and Mcl-1 were earlier demonstrated to be the direct targets of miRNA-29 in many types of cancer tissues and cancers. In both U2OS and SAOS-2 osteoblastic cell types, overexpression of miRNA-29a also downregulated Bcl-2 and Mcl-1, while silencing of miRNA-29a increased their expression. In addition, enhanced expression of miRNA-29a increased the expression of two tumor suppressor genes, E2F1 and E2F3. In summary, data obtained highlight the role of miRNA-29a in the regulation of osteoblastic cell apoptosis by silencing Bcl-2 and Mcl-1 and inducing E2F1 and E2F3 expression.

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References

  1. Ambros V. 2004. The functions of animal microRNAs. Nature. 431, 350–355.

    Article  PubMed  CAS  Google Scholar 

  2. Bartel D.P. 2004. MicroRNAs, genomics, biogenesis, mechanism, and function. Cell. 116, 281–297.

    Article  PubMed  CAS  Google Scholar 

  3. Rogaev E.I., Borinskaia S.A., Islamgulov D.V., Grigorenko A.P. 2008. Human microRNA in norm and pathology. Mol. Biol. (Moscow). 42, 668–680.

    Article  CAS  Google Scholar 

  4. Calin G.A., Croce C.M. 2006. MicroRNA signatures in human cancers. Nature Rev. Cancer. 6, 857–866.

    Article  CAS  Google Scholar 

  5. Negrini M., Nicoloso M.S., Calin G.A. 2009. MicroRNAs and cancer: New paradigms in molecular oncology. Curr. Opin. Cell Biol. 21, 470–479.

    Article  PubMed  CAS  Google Scholar 

  6. Braconi C., Kogure T., Valeri N., Huang N., Nuovo G., Costinean S., Negrini M., Miotto E., Croce C.M., Patel T. 2011. MicroRNA-29 can regulate expression of the long non-coding RNA gene MEG3 in hepatocellular cancer. Oncogene. 30, 1–7.

    Article  Google Scholar 

  7. Garzon R., Heaphy C.E.A., Havelange V., Fabbri M., Volinia S., Tsao T., Zanesi N., Kornblau S.M., Marcucci G., Calin G.A., Andreeff M., Croce C.M. 2009. MicroRNA 29b functions in acute myeloid leukemia. Blood. 17, 5331–5341.

    Article  Google Scholar 

  8. Ottaviani G., Jaffe N. 2010. The epidemiology of osteosarcoma. Cancer Treat. Res. 152, 3–13.

    Article  Google Scholar 

  9. Janeway K.A., Grier H.E. 2010. Sequelae of osteosarcoma medical therapy: A review of rare acute toxicities and late effects. Lancet Oncol. 11, 670–678.

    Article  PubMed  Google Scholar 

  10. Tao J., Chen S., Lee B. 2010. Alteration of Notch signaling in skeletal development and disease. Ann. N.Y. Acad. Sci. 1192, 257–268.

    Article  PubMed  CAS  Google Scholar 

  11. Iorio M.V., Ferracin M., Liu C.G., Veronese A., Spizzo R., Sabbioni S., Magri E., Pedriali M., Fabbri M., Campiglio M., Ménard S., Palazzo J.P., Rosenberg A., Musiani P., Volinia S., Nenci I., Calin G.A., Querzoli P., Negrini M., Croce C.M. 2005. MicroRNA gene expression deregulation in human breast cancer. Cancer Res. 65, 7065–7070.

    Article  PubMed  CAS  Google Scholar 

  12. Pekarsky Y., Santanam U., Cimmino A., Palamarchuk A., Efanov A., Maximov V., Volinia S., Alder H., Liu C.G., Rassenti L., Calin G.A., Hagan J.P., Kipps T., Croce C.M. 2006. Tcl1 expression in chronic lymphocytic leukemia is regulated by miR-29 and miR-181. Cancer Res. 66, 11590–11593.

    Article  PubMed  CAS  Google Scholar 

  13. Porkka K.P., Pfeiffer M.J., Waltering K.K., Vessella R.L., Tammela T.L.J., Visakorpi T. 2007. MicroRNA expression profiling in prostate cancer. Cancer Res. 67, 6130–6135.

    Article  PubMed  CAS  Google Scholar 

  14. Mott J.L., Kobayashi S., Bronk S.F., Gores G.J. 2007. miR-29 regulates Mcl-1 protein expression and apoptosis. Oncogene. 26, 6133–6140.

    Article  PubMed  CAS  Google Scholar 

  15. Stamatopoulos B., Meuleman N., Haibe-Kains B., Saussoy P., van den Neste E., Michaux L., Heimann P., Martiat P., Bron D., Lagneaux L. 2009. MicroRNA-29c and microRNA-223 downregulation has in vivo significance in chronic lymphocytic leukemia and improves disease risk stratification. Blood. 113, 5237–5245.

    Article  PubMed  CAS  Google Scholar 

  16. Wang H., Garzon R., Sun H., Ladner K.J., Singh R., Dahlman J., Cheng A., Hall B.M., Qualman S.J., Chandler D.S., Croce C.M., Guttridge D.C. 2008. NF-kappaB-YY1-miR-29 regulatory circuitry in skeletal myogenesis and rhabdomyosarcoma. Cancer Cell. 14, 369–381.

    Article  PubMed  CAS  Google Scholar 

  17. Fabbri M., Garzon R., Cimmino A., Liu Z.F., Zanesi N., Callegari E., Liu S., Alder H., Costinean S., Fernandez-Cymering C., Volinia S., Guler G., Morrison C.D., Chan K.K., Marcucci G., Calin G.A., Huebner K., Croce C.M. 2007. MicroRNA-29 family reverts aberrant methylation in lung cancer by targeting DNA methyltransferases 3A and 3B. Proc. Natl. Acad. Sci. U. S. A. 104, 15805–15810.

    Article  PubMed  CAS  Google Scholar 

  18. Park S.Y., Lee J.H., Ha M., Nam J.W., Kim V.N. 2008. miR-29 miRNAs activate p53 by targeting p85alpha and CDC42. Nature Struct. Mol. Biol. 16, 23–29.

    Article  Google Scholar 

  19. Lu J., Getz G., Miska E.A., Alvarez-Saavedra E., Lamb J., Peck D., Sweet-Cordero A., Ebert B.L., Mak R.H., Ferrando A.A., Downing J.R., Jacks T., Horvitz H.R., Golub T.R. 2005. MicroRNA expression profiles classify human cancers. Nature. 435, 834–838.

    Article  PubMed  CAS  Google Scholar 

  20. Volinia S., Calin G.A., Liu C.G., Ambs S., Cimmino A., Fabio P., Visone R., Iorio M., Roldo C., Ferracin M., Prueitt R.L., Yanaihara N., Lanza G., Scarpa A., Vecchione A., Negrini M., Harris C.C., Croce C.M. 2006. A microRNA expression signature of human solid tumors defines cancer gene targets. Proc. Natl. Acad. Sci. U. S. A. 103, 2257–2261.

    Article  PubMed  CAS  Google Scholar 

  21. Sieghart W., Losert D., Strommer S., Cejka D., Schmid K., Rasoul-Rockenschaub S., Bodingbauer M., Crevenna R., Monia B.P., Peck-Radosavljevic M., Wacheck V. 2006. Mcl-1 overexpression in hepatocellular carcinoma: A potential target for antisense therapy. J. Hepatol. 44, 151–157.

    Article  PubMed  CAS  Google Scholar 

  22. Zekri A.R.N., Bahnassy A.A., Abdel-Wahab S.A., Khafagy M.M., Loutfy S.A., Radwan H., Shaarawy S.M. 2009. Expression of pro- and anti-inflammatory cytokines in relation to apoptotic genes in Egyptian liver disease patients associated with HCV-genotype-4. J. Gastroenterol. Hepatol. 24, 416–428.

    Article  PubMed  CAS  Google Scholar 

  23. Yip K.W., Reed J.C. 2008. Bcl-2 family proteins and cancer. Oncogene. 27, 6398–406.

    Article  PubMed  CAS  Google Scholar 

  24. Zheng N., Fraenkel E., Pabo C.O., Pavletich N.P. 1999. Structural basis of DNA recognition by the heterodimeric cell cycle transcription factor E2F-DP. Genes Dev. 13, 666–674.

    Article  PubMed  CAS  Google Scholar 

  25. Zwicker J., Liu N., Engeland K., Lucibello F.C., Müller R. 1996. Cell cycle regulation of E2F site occupation in vivo. Science. 271, 1595–1597.

    Article  PubMed  CAS  Google Scholar 

  26. Ogawa H., Ishiguro K., Gaubatz S., Livingston D.M., Nakatani Y. 2002. A complex with chromatin modifiers that occupies E2F- and Myc-responsive genes in G0 cells. Science. 296, 1132–1136.

    Article  PubMed  CAS  Google Scholar 

  27. Xiong Y., Fang J.H., Yun J.P., Yang J., Zhang Y., Jia W.H., Zhuang S.M. 2010. Effects of microRNA-29 on apoptosis, tumorigenicity, and prognosis of hepatocellular carcinoma. Hepatology. 51, 836–845.

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Orthopedics, the No. 401 Hospital of PLA, 22 Minjiang Road, Qingdao, Shandong, 266071, China

    W. Zhang

  2. Department of Oncology, Changzheng Hospital, Second Military University, Shanghai, 200003, China

    J. -X. Qian

  3. Department of Orthopedics, Changhai Hospital, Second Military University, Shanghai, 200433, China

    W. Zhang, H. -L. Yi, Z. -D. Yang, C. -F. Wang, J. -Y. Chen, X. -Z. Wei, Q. Fu & H. Ma

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  1. W. Zhang
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  2. J. -X. Qian
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  3. H. -L. Yi
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  4. Z. -D. Yang
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  9. H. Ma
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Correspondence to H. Ma.

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The article is published in the original.

W. Zhang and J.-X. Qian contributed equally to this work.

W. Zhang and J.-X. Qian are the co-first authors.

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Zhang, W., Qian, J.X., Yi, H.L. et al. The microRNA-29 plays a central role in osteosarcoma pathogenesis and progression. Mol Biol 46, 557–562 (2012). https://doi.org/10.1134/S0026893312040139

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  • DOI: https://doi.org/10.1134/S0026893312040139

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