Targeting of SMAD5 links microRNA-155 to the TGF-beta pathway and lymphomagenesis.

ABSTRACT: The mechanisms by which microRNA dysfunction contributes to the pathogenesis of diffuse large B cell lymphoma (DLBCL) are not well established. The identification of the genes and pathways directly targeted by these small regulatory RNAs is a critical step to advance this field. Using unbiased genome-wide approaches in DLBCL, we discovered that the oncogenic microRNA-155 (miR-155) directly targets the bone morphogenetic protein (BMP)-responsive transcriptional factor SMAD5. Surprisingly, we found that in DLBCL a noncanonical signaling module linking TGF-beta1 signals to SMAD5 is also active. In agreement with these data, miR-155 overexpression rendered DLBCLs resistant to the growth-inhibitory effects of both TGF-beta1 and BMPs, via defective induction of p21 and impaired cell cycle arrest

SUBMITTER: Rai D 

PROVIDER: S-EPMC2840369 | biostudies-literature | 2010 Feb

REPOSITORIES: biostudies-literature