Inhibition of the miR-155 target NIAM phenocopies the growth promoting effect of miR-155 in B-cell lymphoma [L1236]. Homo sapiens

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. Overall design: Gene expression profiles were performed in L1236 Hodgkin lymphoma cell line in 4 samples: L1236 EV (empty pMSCV-PIG vector) total cell lysate, L1236 miR-155-sp (L1236 with miR-155 sponge) total cell lysate, L1236 EV Ago2-IP, L1236 miR-155-sp Ago2-IP. Please note that experiments were performed technically as dual channel (eg, Cy3 and Cy5-labeled samples hybridized to the same array) but the results were processed though they are single channel (total 8 sample records for 4 raw data files; Cy3 and Cy5 signals are calculated). Therefore, raw data files for paired samples (e.g. 'L1236 miR-155-sp Total Cy5' and L1236 miR-155-sp IP Cy3' ) are identical.