Reticuloendotheliosis virus strain T induces miR-155, which targets JARID2 and promotes cell survival.
The oncogenic microRNA miR-155 is upregulated by several oncogenic viruses. The precursor of miR-155, termed bic, was first observed to cooperate with myc in chicken B-cell lymphomas induced by avian leukosis proviral integrations. We identified another oncogenic retrovirus, reticuloendotheliosis virus strain T (REV-T), that upregulates miR-155 in chicken embryo fibroblasts. We also observed very high levels of miR-155 in REV-T-induced B-cell lymphomas. To study the role of miR-155 in these tumors, we identified JARID2/Jumonji, a cell cycle regulator and part of a histone methyltransferase complex, as a target of miR-155. The overexpression of miR-155 decreased levels of endogenous JARID2 mRNA. We confirmed that miR-155 directly targets both human and chicken JARID2 by assaying the repression of reporters containing the JARID2 3'-untranslated regions. Further, the overexpression of a sponge complementary to miR-155 in a tumor cell line increased endogenous JARID2 mRNA levels. The overexpression of JARID2 in chicken fibroblasts led to decreased cell numbers and an increase in apoptotic cells. The overexpression of miR-155 rescued cells undergoing cytopathic effect caused by infection with subgroup B avian retroviruses. Therefore, we propose that miR-155 has a prosurvival function that is mediated through the downregulation of targets including JARID2.
Bolisetty
Mohan T
MT
Department of Biology, Johns Hopkins University, Baltimore, Maryland 21218, USA.
Dy
George
G
Tam
Wayne
W
Beemon
Karen L
KL
D000818:Animals; D002460:Cell Line; D002470:Cell Survival; D002645:Chickens; D005347:Fibroblasts / Q000821:virology; D005786:Gene Expression Regulation; D054884:Host-Pathogen Interactions; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors*; D001356:Reticuloendotheliosis virus / Q000472:pathogenicity*
D035683:MicroRNAs; D009419:Nerve Tissue Proteins