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Circulating microRNA expression is associated with genetic subtype and survival of multiple myeloma

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Abstract

Circulating microRNAs (miRNAs) have shown potential as non-invasive prognostic biomarkers in cancer. Here, we investigated whether miRNAs present in the plasma of multiple myeloma (MM) patients have prognostic utility. We evaluated global miRNA expression profiles in the plasma of 12 multiple myeloma patients and 8 healthy controls using TaqMan Low-Density Arrays. Six miRNAs (miR-148a, miR-181a, miR-20a, miR-221, miR-625, and miR-99b) that were significantly upregulated in MM were selected and further quantified independently by quantitative reverse transcription PCR in plasma from 28 MM patients and 12 healthy controls. Moreover, within the patient group, the expression levels of miR-99b and miR-221 were associated with chromosomal abnormalities t(4; 14) and del(13q), respectively. High levels of miR-20a and miR-148a were related to shorter relapse-free survival. In summary, we have identified aberrant expression of particular circulating miRNAs that are associated with the genetic subtype and survival of MM. These plasma miRNAs have potential as clinical biomarkers in MM.

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References

  1. Lewis BP, Burge CB, Bartel DP. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell. 2005;120(1):15–20.

    Article  PubMed  CAS  Google Scholar 

  2. Li X, Zhang Y, Zhang H, Liu X, Gong T, Li M, et al. miRNA-223 promotes gastric cancer invasion and metastasis by targeting tumor suppressor EPB41L3. Mol Cancer Res. 2011;9(7):824–33.

    Article  PubMed  CAS  Google Scholar 

  3. Jeong HC, Kim EK, Lee JH, Lee JM, Yoo HN, Kim JK. Aberrant expression of let-7a miRNA in the blood of non-small cell lung cancer patients. Mol Med Report. 2011;4(2):383–7.

    PubMed  CAS  Google Scholar 

  4. Yu S, Lu Z, Liu C, Meng Y, Ma Y, Zhao W, et al. miRNA-96 suppresses KRAS and functions as a tumor suppressor gene in pancreatic cancer. Cancer Res. 2010;70(14):6015–25.

    Article  PubMed  CAS  Google Scholar 

  5. Guo X, Guo L, Ji J, Zhang J, Chen X, Cai Q, et al. miRNA-331-3p directly targets E2F1 and induces growth arrest in human gastric cancer. Biochem Biophys Res Commun. 2010;398(1):1–6.

    Article  PubMed  CAS  Google Scholar 

  6. Calin GA, Ferracin M, Cimmino A, Di Leva G, Shimizu M, Wojcik SE, et al. A MicroRNA signature associated with prognosis and progression in chronic lymphocytic leukemia. N Engl J Med. 2005;353(17):1793–801.

    Article  PubMed  CAS  Google Scholar 

  7. Craig VJ, Cogliatti SB, Imig J, Renner C, Neuenschwander S, Rehrauer H, et al. Myc-mediated repression of microRNA-34a promotes high-grade transformation of B-cell lymphoma by dysregulation of FoxP1. Blood. 2011;117(23):6227–36.

    Article  PubMed  CAS  Google Scholar 

  8. Cortez MA, Calin GA. MicroRNA identification in plasma and serum: a new tool to diagnose and monitor diseases. Expert Opin Biol Ther. 2009;9(6):703–11.

    Article  PubMed  CAS  Google Scholar 

  9. Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL, et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci USA. 2008;105(30):10513–8.

    Article  PubMed  CAS  Google Scholar 

  10. Silva J, Garcia V, Zaballos A, Provencio M, Lombardia L, Almonacid L, et al. Vesicle-related microRNAs in plasma of nonsmall cell lung cancer patients and correlation with survival. Eur Respir J. 2011;37(3):617–23.

    Article  PubMed  CAS  Google Scholar 

  11. Chen L, Li C, Zhang R, Gao X, Qu X, Zhao M, et al. miR-17-92 cluster microRNAs confers tumorigenicity in multiple myeloma. Cancer Lett. 2011;309(1):62–70.

    Article  PubMed  CAS  Google Scholar 

  12. Zhang YK, Wang H, Leng Y, Li ZL, Yang YF, Xiao FJ, et al. Overexpression of microRNA-29b induces apoptosis of multiple myeloma cells through down regulating Mcl-1. Biochem Biophys Res Commun. 2011;414(1):233–9.

    Article  PubMed  CAS  Google Scholar 

  13. Pichiorri F, Suh SS, Ladetto M, Kuehl M, Palumbo T, Drandi D, et al. MicroRNAs regulate critical genes associated with multiple myeloma pathogenesis. Proc Natl Acad Sci USA. 2008;105(35):12885–90.

    Article  PubMed  CAS  Google Scholar 

  14. Anderson KC, Alsina M, Bensinger W, Biermann JS, Chanan-Khan A, Comenzo RL, et al. Multiple myeloma. Clinical practice guidelines in oncology. J Natl Compr Canc Netw. 2007;5(2):118–47.

    PubMed  CAS  Google Scholar 

  15. Tusher VG, Tibshirani R, Chu G. Significance analysis of microarrays applied to the ionizing radiation response. Proc Natl Acad Sci USA. 2001;98(9):5116–21.

    Article  PubMed  CAS  Google Scholar 

  16. Ross FM, Ibrahim AH, Vilain-Holmes A, Winfield MO, Chiecchio L, Protheroe RK, et al. Age has a profound effect on the incidence and significance of chromosome abnormalities in myeloma. Leukemia. 2005;19(9):1634–42.

    Article  PubMed  CAS  Google Scholar 

  17. Chng WJ, Santana-Davila R, Van Wier SA, Ahmann GJ, Jalal SM, Bergsagel PL, et al. Prognostic factors for hyperdiploid-myeloma: effects of chromosome 13 deletions and IgH translocations. Leukemia. 2006;20(5):807–13.

    Article  PubMed  CAS  Google Scholar 

  18. Vekemans MC, Lemmens H, Delforge M, Doyen C, Pierre P, Demuynck H, et al. The t(14;20) (q32;q12): a rare cytogenetic change in multiple myeloma associated with poor outcome. Br J Haematol. 2010;149(6):901–4.

    Article  PubMed  CAS  Google Scholar 

  19. Baraniskin A, Kuhnhenn J, Schlegel U, Chan A, Deckert M, Gold R, et al. Identification of microRNAs in the cerebrospinal fluid as marker for primary diffuse large B-cell lymphoma of the central nervous system. Blood. 2011;117(11):3140–6.

    Article  PubMed  CAS  Google Scholar 

  20. Lutherborrow M, Bryant A, Jayaswal V, Agapiou D, Palma C, Yang YH, et al. Expression profiling of cytogenetically normal acute myeloid leukemia identifies microRNAs that target genes involved in monocytic differentiation. Am J Hematol. 2011;86(1):2–11.

    Article  PubMed  CAS  Google Scholar 

  21. Starczynowski DT, Morin R, McPherson A, Lam J, Chari R, Wegrzyn J, et al. Genome-wide identification of human microRNAs located in leukemia-associated genomic alterations. Blood. 2011;117(2):595–607.

    Article  PubMed  CAS  Google Scholar 

  22. Moussay E, Wang K, Cho JH, van Moer K, Pierson S, Paggetti J, et al. MicroRNA as biomarkers and regulators in B-cell chronic lymphocytic leukemia. Proc Natl Acad Sci USA. 2011;108(16):6573–8.

    Article  PubMed  CAS  Google Scholar 

  23. Pesta M, Klecka J, Kulda V, Topolcan O, Hora M, Eret V, et al. Importance of miR-20a expression in prostate cancer tissue. Anticancer Res. 2010;30(9):3579–83.

    PubMed  CAS  Google Scholar 

  24. Lu Y, Thomson JM, Wong HY, Hammond SM, Hogan BL. Transgenic over-expression of the microRNA miR-17-92 cluster promotes proliferation and inhibits differentiation of lung epithelial progenitor cells. Dev Biol. 2007;310(2):442–53.

    Article  PubMed  CAS  Google Scholar 

  25. Tagawa H, Karube K, Tsuzuki S, Ohshima K, Seto M. Synergistic action of the microRNA-17 polycistron and Myc in aggressive cancer development. Cancer Sci. 2007;98(9):1482–90.

    Article  PubMed  CAS  Google Scholar 

  26. Venturini L, Battmer K, Castoldi M, Schultheis B, Hochhaus A, Muckenthaler MU, et al. Expression of the miR-17-92 polycistron in chronic myeloid leukemia (CML) CD34+ cells. Blood. 2007;109(10):4399–405.

    Article  PubMed  CAS  Google Scholar 

  27. Cloonan N, Brown MK, Steptoe AL, Wani S, Chan WL, Forrest AR, et al. The miR-17-5p microRNA is a key regulator of the G1/S phase cell cycle transition. Genome Biol. 2008;9(8):R127.

    Article  PubMed  Google Scholar 

  28. Zhou Y, Chen L, Barlogie B, Stephens O, Wu X, Williams DR, et al. High-risk myeloma is associated with global elevation of miRNAs and overexpression of EIF2C2/AGO2. Proc Natl Acad Sci USA. 2010;107(17):7904–9.

    Article  PubMed  CAS  Google Scholar 

  29. Chi J, Ballabio E, Chen XH, Kusec R, Taylor S, Hay D, et al. MicroRNA expression in multiple myeloma is associated with genetic subtype, isotype and survival. Biol Direct. 2011;6:23.

    Article  PubMed  CAS  Google Scholar 

  30. Zheng B, Liang L, Wang C, Huang S, Cao X, Zha R, et al. MicroRNA-148a suppresses tumor cell invasion and metastasis by downregulating ROCK1 in gastric cancer. Clin Cancer Res. 2011;17(24):7574–83.

    Article  PubMed  CAS  Google Scholar 

  31. Tseng CW, Lin CC, Chen CN, Huang HC, Juan HF. Integrative network analysis reveals active microRNAs and their functions in gastric cancer. BMC Syst Biol. 2011;5:99.

    Article  PubMed  Google Scholar 

  32. Zhou X, Zhao F, Wang ZN, Song YX, Chang H, Chiang Y, et al. Altered expression of miR-152 and miR-148a in ovarian cancer is related. Oncol Rep. 2012;27(2):447–54.

    PubMed  CAS  Google Scholar 

  33. Guo SL, Peng Z, Yang X, Fan KJ, Ye H, Li ZH, et al. miR-148a promoted cell proliferation by targeting p27 in gastric cancer cells. Int J Biol Sci. 2011;7(5):567–74.

    Article  PubMed  CAS  Google Scholar 

  34. Murata T, Takayama K, Katayama S, Urano T, Horie-Inoue K, Ikeda K, et al. miR-148a is an androgen-responsive microRNA that promotes LNCaP prostate cell growth by repressing its target CAND1 expression. Prostate Cancer Prostatic Dis. 2010;13(4):356–61.

    Article  PubMed  CAS  Google Scholar 

  35. Chiecchio L, Protheroe RK, Ibrahim AH, Cheung KL, Rudduck C, Dagrada GP, et al. Deletion of chromosome 13 detected by conventional cytogenetics is a critical prognostic factor in myeloma. Leukemia. 2006;20(9):1610–7.

    Article  PubMed  CAS  Google Scholar 

  36. Paul E, Sutlu T, Deneberg S, Alici E, Bjorkstrand B, Jansson M, et al. Impact of chromosome 13 deletion and plasma cell load on long-term survival of patients with multiple myeloma undergoing autologous transplantation. Oncol Rep. 2009;22(1):137–42.

    PubMed  CAS  Google Scholar 

  37. Park JK, Kogure T, Nuovo GJ, Jiang J, He L, Kim JH, et al. miR-221 silencing blocks hepatocellular carcinoma and promotes survival. Cancer Res. 2011;71(24):7608–16.

    Article  PubMed  CAS  Google Scholar 

  38. Shah MY, Calin GA. MicroRNAs miR-221 and miR-222: a new level of regulation in aggressive breast cancer. Genome Med. 2011;3(8):56.

    Article  PubMed  Google Scholar 

  39. Zhang CZ, Zhang JX, Zhang AL, Shi ZD, Han L, Jia ZF, et al. MiR-221 and miR-222 target PUMA to induce cell survival in glioblastoma. Mol Cancer. 2010;9:229.

    Article  PubMed  Google Scholar 

  40. Sun D, Lee YS, Malhotra A, Kim HK, Matecic M, Evans C, et al. miR-99 family of MicroRNAs suppresses the expression of prostate-specific antigen and prostate cancer cell proliferation. Cancer Res. 2011;71(4):1313–24.

    Article  PubMed  CAS  Google Scholar 

  41. Karlin L, Soulier J, Chandesris O, Choquet S, Belhadj K, Macro M, et al. Clinical and biological features of t(4;14) multiple myeloma: a prospective study. Leuk Lymphoma. 2011;52(2):238–46.

    Article  PubMed  CAS  Google Scholar 

  42. Lionetti M, Biasiolo M, Agnelli L, Todoerti K, Mosca L, Fabris S, et al. Identification of microRNA expression patterns and definition of a microRNA/mRNA regulatory network in distinct molecular groups of multiple myeloma. Blood. 2009;114(25):e20–6.

    Article  PubMed  CAS  Google Scholar 

  43. Hisaoka M, Matsuyama A, Nagao Y, Luan L, Kuroda T, Akiyama H, et al. Identification of altered MicroRNA expression patterns in synovial sarcoma. Genes Chromosomes Cancer. 2011;50(3):137–45.

    Article  PubMed  CAS  Google Scholar 

  44. Feber A, Xi L, Pennathur A, Gooding WE, Bandla S, Wu M, et al. MicroRNA prognostic signature for nodal metastases and survival in esophageal adenocarcinoma. Ann Thorac Surg. 2011;91(5):1523–30.

    Article  PubMed  Google Scholar 

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Acknowledgments

This work was supported by the Hi-Tech Research and Development Program of China (2006AA02Z496).

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The authors declare that they have no competing interests.

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Correspondence to Ren-qian Zhong.

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Jing-jing Huang and Juan Yu contributed equally to this work.

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Huang, Jj., Yu, J., Li, Jy. et al. Circulating microRNA expression is associated with genetic subtype and survival of multiple myeloma. Med Oncol 29, 2402–2408 (2012). https://doi.org/10.1007/s12032-012-0210-3

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  • DOI: https://doi.org/10.1007/s12032-012-0210-3

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