Open AccessOnco‐miR‐155 targets SHIP1 to promote TNFα‐dependent growth of B cell lymphomas
Author(s) -
Pedersen Irene M.,
Otero Dennis,
Kao Elaine,
Miletic Ana V.,
Hother Christoffer,
Ralfkiaer Elisabeth,
Rickert Robert C.,
Gronbaek Kirsten,
David Michael
Publication year - 2009
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.1002/emmm.200900028
Subject(s) - library science , humanities , gerontology , medicine , art , computer science
Non‐coding microRNAs (miRs) are a vital component of post‐transcriptional modulation of protein expression and, like coding mRNAs harbour oncogenic properties. However, the mechanisms governing miR expression and the identity of the affected transcripts remain poorly understood. Here we identify the inositol phosphatase SHIP1 as a bonafide target of the oncogenic miR‐155. We demonstrate that in diffuse large B cell lymphoma (DLBCL) elevated levels of miR‐155, and consequent diminished SHIP1 expression are the result of autocrine stimulation by the pro‐inflammatory cytokine tumour necrosis factor α (TNFα). Anti‐TNFα regimen such as eternacept or infliximab were sufficient to reduce miR‐155 levels and restored SHIP1 expression in DLBCL cells with an accompanying reduction in cell proliferation. Furthermore, we observed a substantial decrease in tumour burden in DLBCL xenografts in response to eternacept. These findings strongly support the concept that cytokine‐regulated miRs can function as a crucial link between inflammation and cancer, and illustrate the feasibility of anti‐TNFα therapy as a novel and immediately accessible (co)treatment for DLBCL.