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Oncogenic microRNA-155 and its target PU.1: an integrative gene expression study in six of the most prevalent lymphomas

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Abstract

The transcription factor PU.1 and its inhibitory microRNA-155 (miR-155) are important regulators of B-cell differentiation. PU.1 downregulation coupled with oncogenic miR-155 upregulation has been reported in lymphoid malignancies; however, these data have not been studied across different subtypes in relation to clinical outcomes. We studied expression of miR-155 and PU.1 in the six most prevalent human B-cell lymphomas (n = 131) including aggressive (DLBCL, HL, MCL) and indolent (B-CLL/SLL, MZL, FL) types. Levels of miR-155 and PU.1 inversely correlated in DLBCL, B-CLL/SLL, and FL tumor tissues. In HL tissues, an exceptionally high level of miR-155 was found in patients with unfavorable responses to first-line therapy and those who had shorter survival times. PU.1 downregulation was noted in B-CLL/SLL samples positive for the adverse prognostic markers CD38 and ZAP-70. Upregulation of miR-155 and downregulation of PU.1 expression are integral aspects of lymphoma biology that could mark aggressive behavior of some, but not all, lymphoma types.

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Acknowledgments

The authors appreciate P. Basova’s help with expression determination, and thank V. Kulvait for discussions on the statistical analyses. Grants: Primary support: GACR P305/12/1033, GAUK-84314; Institutional: UNCE 204021, PRVOUK-P24/LF1/1 and 3, SVV-2014-260033, BIOCEV—Biotechnology and Biomedicine Centre of the Academy of Sciences and Charles University (CZ.1.05/1.1.00/02.0109), from the European Regional Development Fund.

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Authors and Affiliations

  1. Institute of Pathological Physiology, 1st Medical Faculty, Charles University in Prague, U Nemocnice 5, 128 53, Prague, Czech Republic

    Hana Huskova, Jarmila Vargova, Karina Vargova, Nina Dusilkova & Tomas Stopka

  2. 1st Medical Department – Hematology, General Faculty Hospital, U Nemocnice 2, 128 08, Prague, Czech Republic

    Katarina Korecka, Josef Karban, Marek Trneny & Tomas Stopka

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  1. Hana Huskova
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  2. Katarina Korecka
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  4. Jarmila Vargova
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Correspondence to Tomas Stopka.

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Huskova, H., Korecka, K., Karban, J. et al. Oncogenic microRNA-155 and its target PU.1: an integrative gene expression study in six of the most prevalent lymphomas. Int J Hematol 102, 441–450 (2015). https://doi.org/10.1007/s12185-015-1847-4

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  • DOI: https://doi.org/10.1007/s12185-015-1847-4

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