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Lymphoma

MicroRNA-124 links p53 to the NF-κB pathway in B-cell lymphomas

Leukemia volume 29, pages 1868–1874 (2015)Cite this article

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Abstract

The contribution of microRNAs to lymphoma biology is not fully understood. In particular, it remains untested whether microRNA dysregulation could contribute to the emergence of the aggressive subset of B-cell lymphomas that coexpress MYC and BCL2. Here, we identify microRNA-124 (miR-124) as a negative regulator of MYC and BCL2 expression in B-cell lymphomas. Concordantly, stable or transient ectopic expression of miR-124 suppressed cell proliferation and survival, whereas genetic inhibition of this miRNA enhanced the fitness of these tumors. Mechanistically, the activities of miR-124 towards MYC and BCL2 intersect with both oncogenic and tumor-suppressive pathways. In respect to the former, we show that miR-124 directly targets nuclear factor-κB (NF-κB) p65, and using genetic approaches, we demonstrate that this interaction accounts for the miR-124-mediated suppression of MYC and BCL2. We also characterized miR-124 promoter region and identified a functional p53 binding site. In agreement with this finding, endogenous or ectopic expression of wild-type, but not mutant, p53 increased miR-124 levels and suppressed p65, MYC and BCL2. Our data unveil an miRNA-dependent regulatory circuitry that links p53 to the NF-κB pathway, which when disrupted in B-cell lymphoma may be associated with aberrant coexpression of MYC and BCL2 and poor prognosis.

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Acknowledgements

We thank Dr Kyung Lib Jang (Pusan National University) for the WT and MUT (R248Q) p53 constructs. This work was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2013R1A1A2008838) to S-WK and RCTA was funded by NCI/NIH R01-CA138747 and Veterans Administration Merit Award (I01-BX001882).

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Author notes

  1. D Jeong and J Kim: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Biological Sciences, Pusan National University, Pusan, Korea

    D Jeong, J Kim, J Nam & S-W Kim

  2. Department of Statistics, Pusan National University, Pusan, Korea

    H Sun

  3. Department of Radiation Oncology, Yonsei University, Seoul, Korea

    Y-H Lee

  4. Department of Anatomy, Yeungnam University, Daegu, Korea

    T-J Lee

  5. Division of Hematology and Medical Oncology, Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA

    R C T Aguiar

  6. South Texas Veterans Health Care System, Audie Murphy VA Hospital, San Antonio, TX, USA

    R C T Aguiar

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  1. D Jeong
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Correspondence to S-W Kim.

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Jeong, D., Kim, J., Nam, J. et al. MicroRNA-124 links p53 to the NF-κB pathway in B-cell lymphomas. Leukemia 29, 1868–1874 (2015). https://doi.org/10.1038/leu.2015.101

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