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

// Izabella Slezak-Prochazka 1,2,* , Joost Kluiver 1,* , Debora de Jong 1 , Katarzyna Smigielska-Czepiel 1 , Gertrud Kortman 1 , Melanie Winkle 1 , Bea Rutgers 1 , Jasper Koerts 1 , Lydia Visser 1 , Arjan Diepstra 1 , Bart-Jan Kroesen 1 and Anke van den Berg 1 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.