International Journal of Hematology

, Volume 107, Issue 3, pp 345–354 | Cite as

Enforced expression of MIR142, a target of chromosome translocation in human B-cell tumors, results in B-cell depletion

  • Kodai Kuriyama
  • Yutaka Enomoto
  • Ritsuro Suzuki
  • Jyuri Watanuki
  • Hiroki Hosoi
  • Yusuke Yamashita
  • Shogo Murata
  • Toshiki Mushino
  • Shinobu Tamura
  • Nobuyoshi Hanaoka
  • Martin Dyer
  • Reiner Siebert
  • Hiroshi Kiyonari
  • Hideki Nakakuma
  • Toshio Kitamura
  • Takashi Sonoki
Original Article


MicroRNA142 (MIR142) is a target of chromosome translocations and mutations in human B-cell lymphomas. We analyzed an aggressive B-cell lymphoma carrying t(8;17)(q24;q22) and t(6;14)(p21;q32), and sought to explore the role(s) of MIR142 in lymphomagenesis. t(8;17)(q24;q22) involved MYC on 8q24 and pri-MIR142 on 17q22. MYC was activated by a promoter substitution by t(8;17)(q24;q22). t(8;17)(q24;q22) was an additional event after t(6;14) (p21;q32), which caused the over-expression of CCND3. Southern blot analyses revealed that the MIR142 locus was deleted from the affected allele, whereas Northern analyses showed over-expression of MIR142 in tumor cells. Although previous studies reported an over-expression of mutations in MIR142 in B-cell lymphomas, limited information is available on the functions of MIR142 in lymphomagenesis. Therefore, we generated bone marrow transplantation (BMT) and transgenic (Eμ/mir142) mice, which showed enforced expression in hematopoietic progenitor cells and B cells, respectively. BMT mice showed decreased numbers of all lineage-positive cells, particularly B cells, in peripheral blood. Eμ/mir142 mice showed decreased numbers of IgM-positive splenocytes, and exhibited altered B-cell phenotypic changes induced by lipopolysaccharide. Our results suggest that over-expression of MIR142 alters B-cell differentiation, implying multi-step lymphomagenesis together with MYC activation and CCND3 over-expression.


MicroRNA142 Chromosome translocation B-lymphoma MYC CCND3 



This work was supported by Grants from the MIYAJIMA Foundation, Yatsushiro, Japan, the Ministry of Education, Culture, Sports, Science, and Technology (MEXT), Japan (no. 25461433), and Wakayama Medical University (a Research Grant on Priority Areas, 2014).

Compliance with ethical standards

Conflict of interest

None of the authors have a COI with regards to this work.

Supplementary material

12185_2017_2360_MOESM1_ESM.ppt (138 kb)
Supplementary Figure 1. Partial sequences of inversion (A), derivative 8 (B), and derivative 17 (C) breakpoints are shown. The three breakpoint alignments were registered in GenBank as accession numbers AB213411, AB213412, and AB213413, respectively. The underlined nucleotides were duplicated at breakpoints. The putative activation-induced deaminase (AID) target sequences are shown in bold italic characters. Capital and lowercase characters represent nucleotides derived from chromosomes 8 and 17, respectively (PPT 138 kb)
12185_2017_2360_MOESM2_ESM.ppt (484 kb)
Supplementary Figure 2. (A) Enzyme maps of germ and translocation alleles are shown. Solid bars under enzyme maps indicate probes. Numbers (#1–#2’) show breakpoints. G; BglII, E; EcoRI, H; HindIII. The BE0.75, BE0.4, and ES0.3 probes were prepared from the LDI-PCR products. (B) Southern blot analyses of the probes derived from the 8q24 and 17q22 breakpoints. (Upper panel) Rearranged bands detected by the MYC-I probe showed co-migration with rearranged bands detected by the BE0.75 probe. The dotted arrows indicate rearranged bands. (Lower panel) Co-migration studies using the MYC-SS, BE0.4, and ES0.3 probes. Solid arrows are rearranged bands detected by the MYC-SS and ES0.3 probes. Dotted arrows are rearranged bands detected by the MYC-SS and BE0.4 probes. The rearranged bands detected by the MYC-SS probe exhibited co-migration with the respective rearranged bands detected by the BE0.4 and ES0.3 probes (PPT 483 kb)
12185_2017_2360_MOESM3_ESM.ppt (302 kb)
Supplementary Figure 3. (A) Results of 3’ RACE. (Upper left) A 1,446-bp product was yielded by 3’ RACE from HL60. The DNA size marker is a λ/HindIII digest. Sequence data is available as accession no. LC194526. (B) Relative positions of the 17q22 breakpoints, 3’ RACE product, and MIR142. The solid arrow and its direction indicate 17q22 and telomeric orientation, respectively. Arrow heads represent two 17q22 breakpoints, which were cloned in this study. The asterisk is the previously cloned 17q22 breakpoint (accession number M31826.1). The dotted arrow indicates the 3’ RACE product. The three 17q22 breakpoints truncated the genomic locus of the transcript. (C) An enzyme map of the MIR142 locus and probes used are illustrated. The 5’-probe was set upstream of MIR142. The box and bar in the box are the MIR142-containing transcript and position of the mature MIR142 sequence, respectively. G; Bgl II and E; EcoRI. (D) Southern blot analysis of the MIR142 locus. A Southern blot using the 5’-probe suggested increased copy numbers upstream of MIR142. The EheI/PstI probe recognizing MIR142 exhibited equal intensity to the germ line control. The 2p13 probe is EH3.0/PstI 0.9, which recognized the BCL11A locus serving as the loading control [35]. Lane 1; analyzed tumor cells, lane 2; germ line control (PPT 302 kb)
12185_2017_2360_MOESM4_ESM.ppt (248 kb)
Supplementary Table 4 (PPT 247 kb)


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Copyright information

© The Japanese Society of Hematology 2017

Authors and Affiliations

  • Kodai Kuriyama
    • 1
  • Yutaka Enomoto
    • 2
    • 9
  • Ritsuro Suzuki
    • 3
  • Jyuri Watanuki
    • 1
  • Hiroki Hosoi
    • 1
  • Yusuke Yamashita
    • 1
  • Shogo Murata
    • 1
  • Toshiki Mushino
    • 1
  • Shinobu Tamura
    • 1
  • Nobuyoshi Hanaoka
    • 1
  • Martin Dyer
    • 4
  • Reiner Siebert
    • 5
    • 6
  • Hiroshi Kiyonari
    • 7
    • 8
  • Hideki Nakakuma
    • 1
  • Toshio Kitamura
    • 2
  • Takashi Sonoki
    • 1
  1. 1.Hematology/OncologyWakayama Medical UniversityWakayamaJapan
  2. 2.Division of Cellular Therapy and Division of Stem Cell Signaling, The Institute of Medical ScienceThe University of TokyoTokyoJapan
  3. 3.Hematology and OncologyShimane Medical UniversityShimaneJapan
  4. 4.Department of Cancer Studies and Molecular Medicine, Leicester Medical SchoolUniversity of LeicesterLeicesterUK
  5. 5.Institute of Human GeneticsChristian Albrechts University KielKielGermany
  6. 6.Institute of Human GeneticsUniversity of Ulm and University of Ulm Medical CenterUlmGermany
  7. 7.Animal Resource Development UnitRIKEN Center for Life Science TechnologiesKobeJapan
  8. 8.Genetic Engineering TeamRIKEN Center for Life Science TechnologiesKobeJapan
  9. 9.Laboratory of Cell Growth and Differentiation, Institute of Molecular and Cellular BiosciencesThe University of TokyoTokyoJapan

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