Oncotarget

Research Papers:

Inhibition of the miR-155 target NIAM phenocopies the growth promoting effect of miR-155 in B-cell lymphoma

Izabella Slezak-Prochazka, Joost Kluiver, Debora de Jong, Katarzyna Smigielska-Czepiel, Gertrud Kortman, Melanie Winkle, Bea Rutgers, Jasper Koerts, Lydia Visser, Arjan Diepstra, Bart-Jan Kroesen and Anke van den Berg _

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Oncotarget. 2016; 7:2391-2400. https://doi.org/10.18632/oncotarget.6165

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Abstract

Izabella Slezak-Prochazka1,2,*, Joost Kluiver1,*, Debora de Jong1, Katarzyna Smigielska-Czepiel1, Gertrud Kortman1, Melanie Winkle1, Bea Rutgers1, Jasper Koerts1, Lydia Visser1, Arjan Diepstra1, Bart-Jan Kroesen1 and Anke van den Berg1

1 Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands

2 Biosystems Group, Institute of Automatic Control, Silesian University of Technology, Gliwice, Poland

* These authors have contributed equally to this work

Correspondence to:

Anke van den Berg, email:

Keywords: B-cell lymphoma, NIAM, Ago2-IP, miR-155, TBRG1

Received: July 16, 2015 Accepted: October 04, 2015 Published: October 19, 2015

Abstract

Several studies have indicated an important role for miR-155 in the pathogenesis of B-cell lymphoma. Highly elevated levels of miR-155 were indeed observed in most B-cell lymphomas with the exception of Burkitt lymphoma (BL). However, the molecular mechanisms that underlie the oncogenic role of miR-155 in B-cell lymphoma are not well understood. To identify the miR-155 targets relevant for B-cell lymphoma, we performed RNA immunoprecipitation of Argonaute 2 in Hodgkin lymphoma (HL) cells upon miR-155 inhibition and in BL cells upon ectopic expression of miR-155. We identified 54 miR-155-specific target genes in BL cells and confirmed miR-155 targeting of DET1, NIAM, TRIM32, HOMEZ, PSIP1 and JARID2. Five of these targets are also regulated by endogenous miR-155 in HL cells. Both overexpression of miR-155 and inhibition of expression of the novel miR-155 target gene NIAM increased proliferation of BL cells. In primary B-cell lymphoma NIAM-positive cases have significant lower levels of miR-155 as compared to NIAM-negative cases, suggesting that NIAM is also regulated by miR-155 in primary B-cell lymphoma. Thus, our data indicate an oncogenic role for miR-155 in B-cell lymphoma which involves targeting the tumor suppressor NIAM.


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