International Journal of Hematology

DOI: 10.1007/s12185-017-2360-8 Pages: 345-354

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

1. Wakayama Medical University, Hematology/Oncology

2. The University of Tokyo, Division of Cellular Therapy and Division of Stem Cell Signaling, The Institute of Medical Science

3. Shimane Medical University, Hematology and Oncology

4. University of Leicester, Department of Cancer Studies and Molecular Medicine, Leicester Medical School

5. Christian Albrechts University Kiel, Institute of Human Genetics

6. University of Ulm and University of Ulm Medical Center, Institute of Human Genetics

7. RIKEN Center for Life Science Technologies, Animal Resource Development Unit

8. RIKEN Center for Life Science Technologies, Genetic Engineering Team

9. The University of Tokyo, Laboratory of Cell Growth and Differentiation, Institute of Molecular and Cellular Biosciences

Correspondence to:
Takashi Sonoki
Tel: (+81-73) 441-0665



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.

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