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

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

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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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.

Original languageEnglish
Pages (from-to)2391-2400
Number of pages10
JournalOncotarget
Volume7
Issue number3
DOIs
Publication statusPublished - 19-Jan-2016

Keywords

  • B-cell lymphoma
  • NIAM
  • Ago2-IP
  • miR-155
  • TBRG1
  • INDUCED CYTIDINE DEAMINASE
  • NUCLEAR INTERACTOR
  • HODGKIN LYMPHOMA
  • BURKITT-LYMPHOMA
  • GENE-EXPRESSION
  • MICRORNA-155
  • ACTIVATION
  • MDM2
  • ARF
  • MYC

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