Mir-155 Enhances B-Cell Lymphoma Growth By Targeting TBRG1

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, TBRG1 (NIAM1), 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 miR-155 target gene TBRG1 increased proliferation of BL cells. In primary B-cell lymphoma TBRG1-positive cases have significant lower levels of miR-155 as compared to TBRG1-negative cases, suggesting that TBRG1 is also regulated by miR-155 in primary B-cell lymphoma. Thus, our data indicate that miR-155 plays an oncogenic role in B-cell lymphoma by targeting the tumor suppressor TBRG1.