title: Sponges against miR-19 and miR-155 reactivate the p53-Socs1 axis in hematopoietic cancers.
abstract: Normal cell proliferation is controlled by a balance between signals that promote or halt cell proliferation. Micro RNAs are emerging as key elements in providing fine signal balance in different physiological situations. Here we report that STAT5 signaling induces the miRNAs miR-19 and miR-155, which potentially antagonize the tumor suppressor axis composed by the STAT5 target gene SOCS1 (suppressor of cytokine signaling-1) and its downstream effector p53. MiRNA sponges against miR-19 or miR-155 inhibit the functions of these miRNAs and potentiate the induction of SOCS1 and p53 in mouse leukemia cells and in human myeloma cells. Adding a catalytic RNA motif of the hammerhead type within miRNA sponges against miR-155 leads to decreased miR-155 levels and increased their ability of inhibiting cell growth and cell migration in myeloma cells. The results indicate that antagonizing miRNA activity can reactivate tumor suppressor pathways downstream cytokine stimulation in tumor cells.
authors: Département de biochimie et médecine moléculaire, Université de Montréal, C.P. 6128, Succ. Centre-Ville, Montréal, Québec H3C 3J7, Canada.
authors: Lian
authors: L
authors: Mignacca
authors: Département de biochimie et médecine moléculaire, Université de Montréal, C.P. 6128, Succ. Centre-Ville, Montréal, Québec H3C 3J7, Canada.
authors: Emmanuelle
authors: E
authors: Saint-Germain
authors: Département de biochimie et médecine moléculaire, Université de Montréal, C.P. 6128, Succ. Centre-Ville, Montréal, Québec H3C 3J7, Canada.
authors: Alexandre
authors: A
authors: Benoit
authors: Département de biochimie et médecine moléculaire, Université de Montréal, C.P. 6128, Succ. Centre-Ville, Montréal, Québec H3C 3J7, Canada.
authors: Véronique
authors: V
authors: Bourdeau
authors: Département de biochimie et médecine moléculaire, Université de Montréal, C.P. 6128, Succ. Centre-Ville, Montréal, Québec H3C 3J7, Canada.
authors: Alejandro
authors: A
authors: Moro
authors: Département de biochimie et médecine moléculaire, Université de Montréal, C.P. 6128, Succ. Centre-Ville, Montréal, Québec H3C 3J7, Canada. Electronic address: g.ferbeyre@umontreal.ca.
authors: Gerardo
authors: G
authors: Ferbeyre
mesh_terms: D000818:Animals; D006801:Humans; D007938:Leukemia / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009101:Multiple Myeloma / Q000235:genetics / Q000378:metabolism*; D000067996:RAW 264.7 Cells; D016337:RNA, Catalytic / Q000096:biosynthesis* / Q000235:genetics; D012334:RNA, Neoplasm / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000071222:Suppressor of Cytokine Signaling 1 Protein / Q000235:genetics / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: C524942:MIRN155 microRNA, human; C549214:MIRN19A microRNA, human; C561642:MIRN19 microRNA, mouse; D035683:MicroRNAs; C532623:Mirn155 microRNA, mouse; D016337:RNA, Catalytic; D012334:RNA, Neoplasm; C108944:SOCS1 protein, human; C491590:Socs1 protein, mouse; D000071222:Suppressor of Cytokine Signaling 1 Protein; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C427204:hammerhead ribozyme
keywords: Catalytic sponges; SOCS1; miR-155; miR-19; miRNA sponges; p53