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microRNA in Malignant Lymphoma

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microRNA: Cancer

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 889))

Abstract

microRNAs (miRNAs) are noncoding regulatory RNAs usually consisting of 20–24 nucleotides. During the past decade, increases and decreases in miRNA expression have been shown to associate with various types of diseases, including cancer. Over 4500 miRNAs have been identified in humans, and it is known that nearly all human protein-encoding genes can be controlled by miRNAs in both healthy and malignant cells. Detailed genome-wide miRNA expression analysis has been performed in various malignant lymphoma subtypes, and these analyses have led to the discovery of subtype-specific miRNA alterations. In this chapter, I describe several key miRNAs and their targets in distinct malignant lymphoma subsets and their roles in their pathogenesis, studies of which will lead new therapeutic strategies against aggressive lymphomas.

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References

  1. Jaffe ES, Harris NL, Stein H, Campo E, Pileri SA, Swerdlow SH. Introduction and over review of the classification of the lymphoid neoplasms. In: Swerdloe AH, Campo E, Harris NL, Jaffe ES, Stein H, Thiele J, Vardiman JW, editors. World health classification of tumors. Pathology & Genetics of tumors of haematopoietic and lymphoid tissues. Washington/Lyon: IARC press; 2008. p. 158–78.

    Google Scholar 

  2. Calin GA, Croce CM. MicroRNA signatures in human cancers. Nat Rev Cancer. 2006;6:857–66.

    Article  CAS  PubMed  Google Scholar 

  3. Baer C, Claus R, Plass C. Genome-wide epigenetic regulation of miRNAs in cancer. Cancer Res. 2013;73:473–7.

    Article  CAS  PubMed  Google Scholar 

  4. Migliazza A, Bosch F, Komatsu H, et al. Nucleotide sequence, transcription map, and mutation analysis of the 13q14 chromosomal region deleted in B-cell chronic lymphocytic leukemia. Blood. 2001;97:2098–104.

    Article  CAS  PubMed  Google Scholar 

  5. Calin GA, Dumitru CD, Shimizu M, et al. Frequent deletions and down-regulation of micro- RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci U S A. 2002;99:15524–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Ota A, Tagawa H, Karnan S, et al. Identification and characterization of a novel gene, C13orf25, as a target for 13q31-q32 amplification in malignant lymphoma. Cancer Res. 2004;64:3087–95.

    Article  CAS  PubMed  Google Scholar 

  7. Tagawa H, Seto M. A microRNA cluster as a target of genomic amplification in malignant lymphoma. Leukemia. 2005;19:2013–6.

    Article  CAS  PubMed  Google Scholar 

  8. He L, Thomson JM, Hemann MT, et al. A microRNA polycistron as a potential human oncogene. Nature. 2005;435:828–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Ventura A, Young AG, Winslow MM, et al. Targeted deletion reveals essential and overlapping functions of the miR-17-92 family of miRNA clusters. Cell. 2008;132:875–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Xiao C, Srinivasan L, Calado DP, et al. Lymphoproliferative disease and autoimmunity in mice with elevated miR-17-92 expression in lymphocytes. Nat Immunol. 2008;9:405–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Inomata M, Tagawa H, Guo Y-M, et al. MicroRNA-17-92 downregulates expression of distinct targets in different B-cell lymphoma subtypes. Blood. 2009;113:396–402.

    Article  CAS  PubMed  Google Scholar 

  12. Olive V, Bennett MJ, Walker JC, et al. miR-19 is a key oncogenic component of mir-17-92. Genes Dev. 2009;23:2839–49.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Mu P, Han YC, Betel D, Yao E, et al. Genetic dissection of the miR-17-92 cluster of microRNAs in Myc-induced B-cell lymphomas. Genes Dev. 2009;23:2806–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Cimmino A, Calin GA, Fabbri M, Iorio MV, Ferracin M, Shimizu M, Wojcik SE, Aqeilan RI, Zupo S, Dono M, Rassenti L, Alder H, Volinia S, Liu CG, Kipps TJ, Negrini M, Croce CM. miR-15 and miR-16 induce apoptosis by targeting BCL2. Proc Natl Acad Sci U S A. 2005;102(39):13944–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Linsley PS, Schelter J, Burchard J, Kibukawa M, Martin MM, Bartz SR, Johnson JM, Cummins JM, Raymond CK, Dai H, Chau N, Cleary M, Jackson AL, Carleton M, Lim L. Transcripts targeted by the microRNA-16 family cooperatively regulate cell cycle progression. Mol Cell Biol. 2007;27(6):2240–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Bonci D, Coppola V, Musumeci M, Addario A, Giuffrida R, Memeo L, D’Urso L, Pagliuca A, Biffoni M, Labbaye C, Bartucci M, Muto G, Peschle C, De Maria R. The miR-15a and miR-16-1 cluster controls prostate cancer by targeting multiple oncogenic activities. Nat Med. 2008;14(11):1271–7.

    Article  CAS  PubMed  Google Scholar 

  17. Liu Q, Fu H, Sun F, Zhang H, Tie Y, Zhu J, Xing R, Sun Z, Zheng X. miR-16 family induces cell cycle arrest by regulating multiple cell cycle genes. Nucleic Acids Res. 2008;36(16):5391–404.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Pothof J, Verkaik NS, van IJcken W, Wiemer EA, Ta VT, van der Horst GT, Jaspers NG, van Gent DC, Hoeijmakers JH, Persengiev SP. MicroRNA-mediated gene silencing modulates the UV-induced DNA-damage response. EMBO J. 2009;28(14):2090–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Zhang X, Wan G, Mlotshwa S, Vance V, Berger FG, Chen H, Lu X. Oncogenic Wip1 phosphatase is inhibited by miR-16 in the DNA damage signaling pathway. Cancer Res. 2010;70(18):7176–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Ofir M, Hacohen D, Ginsberg D. miR-15 and miR-16 are direct transcriptional targets of E2F1 that limit E2F-induced proliferation by targeting cyclin E. Mol Cancer Res. 2011;9(4):440–7.

    Article  CAS  PubMed  Google Scholar 

  21. Rivas MA, Venturutti L, Huang YW, Schillaci R, Huang THM, Elizalde PV. Downregulation of the tumor-suppressor miR-16 via progestin-mediated oncogenic signaling contributes to breast cancer development. Breast Cancer Res. 2012;14(3):R77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Pouliot LM, Chen YC, Bai J, Guha R, Martin SE, Gottesman MM, Hall MD. Cisplatin sensitivity mediated by WEE1 and CHK1 is mediated by miR-155 and the miR-15 family. Cancer Res. 2012;72(22):5945–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Kim KT, Carroll AP, Mashkani B, Cairns MJ, Small D, Scott RJ. MicroRNA-16 is down-regulated in mutated FLT3 expressing murine myeloid FDC-P1 cells and Interacts with Pim-1. PLoS One. 2012;7(9), e44546.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Zhou R, Li X, Hu G, Gong AY, Drescher KM, Chen XM. MiR-16 targets transcriptional corepressor SMRT and modulates NF-kappaB-regulated transactivation of interleukin-8 gene. PLoS One. 2012;7(1), e30772.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Young LE, Moore AE, Sokol L, Meisner-Kober N, Dixon DA. The mRNA stability factor HuR inhibits MicroRNA-16 targeting of COX-2. Mol Cancer Res. 2012;10(1):167–80.

    Article  CAS  PubMed  Google Scholar 

  26. Rissland OS, Hong S-L, Bartel DP. MicroRNA destabilization enables dynamic regulation of the miR-16 family in response to cell-cycle changes. Mol Cell. 2011;43(6):993–1004.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Alizadeh AA, Eisen MB, Davis RE, et al. Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature. 2000;403:503–11.

    Article  CAS  PubMed  Google Scholar 

  28. Lenz G, Wright GW, Emre NC, et al. Molecular subtypes of diffuse large B-cell lymphoma arise by distinct genetic pathways. Proc Natl Acad Sci U S A. 2008;105:13520–5.29.

    Google Scholar 

  29. Malumbres R, Sarosiek KA, Cubedo E, Ruiz JW, Jiang X, Gascoyne RD, et al. Differentiation stage-specific expression of microRNAs in B lymphocytes and diffuse large B-cell lymphomas. Blood. 2009;113:3754–3764.

    Google Scholar 

  30. Montes-Moreno S, Martinez N, et al. miRNA expression in diffuse large B-cell lymphoma treated with chemoimmunotherapy. Blood. 2011;118:1034–40.

    Google Scholar 

  31. Alencar AJ, Malumbres R, Kozloski GA, et al. MicroRNAs are independent predictors of outcome in diffuse large B-cell lymphoma patients treated with R-CHOP. Clin Cancer Res. 2011;17:4125–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Merkel O, Hamacher F, Laimer D, et al. Identification of differential and functionally active miRNAs in both anaplastic lymphoma kinase (ALK) + and ALK- anaplastic large-cell lymphoma. Proc Natl Acad Sci U S A. 2010;107:16228–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Liu C, Iqbal J, Teruya-Feldstein J, Shen Y, Dabrowska MJ, Dybkaer K, et al. MicroRNA expression profiling identifies molecular signatures associated with anaplastic large cell lymphoma. Blood. 2013;122(12):2083–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Spaccarotella E, Pellegrino E, Ferracin M, Ferreri C, Cuccuru G, Liu C, et al. STAT3-mediated activation of microRNA cluster 17 ~ 92 promotes proliferation and survival of ALK positive anaplastic large cell lymphoma. Haematologica. 2013;99(1):116–24.

    Article  PubMed  Google Scholar 

  35. Zhu H, Vishwamitra D, Curry CV, Manshouri R, Diao L, Khan A, et al. NPM-ALK up-regulates iNOS expression through a STAT3/microRNA-26a-dependent mechanism. J Pathol. 2013;230(1):82–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Matsuyama H, Suzuki HI, Nishimori H, Noguchi M, Yao T, Komatsu N, et al. miR-135b mediates NPM-ALK-driven oncogenicity and renders IL-17-producing immunophenotype to anaplastic large cell lymphoma. Blood. 2011;118(26):6881–92.

    Article  CAS  PubMed  Google Scholar 

  37. Nakashima Y, Tagawa H, Suzuki R, et al. Genome-wide array-based comparative genomic hybridization of natural killer cell lymphoma/leukemia: different genomic alteration patterns of aggressive NK-cell leukemia and extranodal NK/T lymphoma, nasal type. Genes Chromosomes Cancer. 2005;19:247–55.

    Article  Google Scholar 

  38. Yamanaka Y, Tagawa H, Takahashi N, et al. Aberrant overexpression of microRNAs activate AKT signaling via down-regulation of tumor suppressors in natural killer-cell lymphoma/leukemia. Blood. 2009;114:3265–75.

    Article  CAS  PubMed  Google Scholar 

  39. Watanabe A, Tagawa H, Yamashita J, Teshima K, Nara M, Iwamoto K, et al. The role of microRNA-150 as a tumor suppressor in malignant lymphoma. Leukemia. 2011;25(8):1324–34.

    Article  CAS  PubMed  Google Scholar 

  40. Robbiani DF, Bothmer A, Callen E, et al. AID is required for the chromosomal breaks in c-myc that lead to c-myc/IgH translocations. Cell. 2008;135:1028–38.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Dorsett Y, McBride KM, Jankovic M, et al. MicroRNA-155 suppresses activation-induced cytidine deaminase-mediated Myc-Igh translocation. Immunity. 2008;8:630–8.

    Article  Google Scholar 

  42. Lenze D, Leoncini L, Hummel M, et al. The different epidemiologic subtypes of Burkitt lymphoma share a homogenous micro RNA profile distinct from diffuse large B-cell lymphoma. Leukemia. 2011;25:1869–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Zhao JJ, Lin J, Lwin T, et al. microRNA expression profile and identification of miR-29 as a prognostic marker and pathogenetic factor by targeting CDK6 in mantle cell lymphoma. Blood. 2010;115:2630–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Navarro A, Beà S, Fernández V, et al. MicroRNA expression, chromosomal alterations, and immunoglobulin variable heavy chain hypermutations in mantle cell lymphomas. Cancer Res. 2009;69:7071–8.

    Article  CAS  PubMed  Google Scholar 

  45. Di Lisio L, Gómez-López G, Sánchez-Beato M, et al. Mantle cell lymphoma: transcriptional regulation by microRNAs. Leukemia. 2010;24:1335–42.

    Article  PubMed  Google Scholar 

  46. Teshima K, Nara M, Watanabe A, et al. Dysregulation of BMI1 and microRNA-16 collaborate to enhance an anti-apoptotic potential in the side population of refractory mantle cell lymphoma. Oncogene. 2014;33(17):2191–203.

    Article  CAS  PubMed  Google Scholar 

  47. Chen RW, Bemis LT, Amato CM, et al. Truncation in CCND1 mRNA alters miR-16-1 regulation in mantle cell lymphoma. Blood. 2008;112:822–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Zhang X, Zhao X, Fiskus W, et al. Coordinated silencing of MYC-mediated miR-29 by HDAC3 and EZH2 as a therapeutic target of histone modification in aggressive B-cell lymphomas. Cancer Cell. 2012;22:506–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Ito M, Teshima K, Ikeda S, Watanabe A, Nara M, Kitadate A, et al. MicroRNA-150 inhibits tumor invasion and metastasis by targeting the chemokine receptor CCR6 in advanced cutaneous T-cell lymphoma. Blood. 2014;123(10):1499–511

    Google Scholar 

  50. Wang W, Corrigan-Cummins M, Hudson J, et al. MicroRNA profiling of follicular lymphoma identifies microRNAs related to cell proliferation and tumor response. Haematologica. 2012;97:586–94.

    Google Scholar 

  51. Karube K, Guo Y, Suzumiya J, et al. CD10-MUM1+ follicular lymphoma lacks BCL2 gene translocation and shows characteristic biologic and clinical features. Blood. 2007;109:3076–9.

    CAS  PubMed  Google Scholar 

  52. Leich E, Zamo A, Horn H, et al. MicroRNA profiles of t(14;18)-negative follicular lymphoma support a late germinal center B-cell phenotype. Blood. 2011;118:5550–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Liu TY, Chen SU, Kuo SH, Cheng AL, Lin CW. E2A-positive gastric MALT lymphoma has weaker plasmacytoid infiltrates and stronger expression of the memory B-cell-associated miR-223: possible correlation with stage and treatment response. Mod Pathol. 2010;23:1507–17.

    Article  CAS  PubMed  Google Scholar 

  54. Craig VJ, Cogliatti SB, Imig J, et al. Myc-mediated repression of microRNA-34a promotes high-grade transformation of B-cell lymphoma by dysregulation of FoxP1. Blood. 2011;117:6227–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Arribas AJ, Campos-Martín Y, Gómez-Abad C, et al. Nodal marginal zone lymphoma: gene expression and miRNA profiling identify diagnostic markers and potential therapeutic targets. Blood. 2012;119:e9–21.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Hematology, Nephrology, and Rheumatology, Akita University Graduate School of Medicine, Akita, 0108543, Japan

    Hiroyuki Tagawa M.D.

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  1. Hiroyuki Tagawa M.D.
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Correspondence to Hiroyuki Tagawa M.D. .

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Editors and Affiliations

  1. Department of Physiology, Columbia University Medical Center, New York, New York, USA

    Gaetano Santulli

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Tagawa, H. (2015). microRNA in Malignant Lymphoma. In: Santulli, G. (eds) microRNA: Cancer. Advances in Experimental Medicine and Biology, vol 889. Springer, Cham. https://doi.org/10.1007/978-3-319-23730-5_3

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