Open AccessVav1 is necessary for PU .1 mediated upmodulation of miR‐29b in acute myeloid leukaemia‐derived cells
Author(s) -
Vezzali Federica,
Grassilli Silvia,
Lambertini Elisabetta,
Brugnoli Federica,
Patergnani Simone,
Nika Ervin,
Piva Roberta,
Pinton Paolo,
Capitani Silvano,
Bertagnolo Valeria
Publication year - 2018
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13594
Subject(s) - cancer research , hypomethylating agent , promoter , transcription (linguistics) , myeloid , medicine , biology , chemistry , gene , gene expression , genetics , dna methylation , linguistics , philosophy
It has been recently demonstrated that high pre‐treatment levels of miR‐29b positively correlated with the response of patients with acute myeloid leukaemia ( AML ) to hypomethylating agents. Upmodulation of miR‐29b by restoring its transcriptional machinery appears indeed a tool to improve therapeutic response in AML . In cells from acute promyelocytic leukaemia ( APL ), miR‐29b is regulated by PU .1, in turn upmodulated by agonists currently used to treat APL . We explored here the ability of PU .1 to also regulate miR‐29b in non‐ APL cells, in order to identify agonists that, upmodulating PU .1 may be beneficial in hypomethylating agents‐based therapies. We found that PU .1 may regulate miR‐29b in the non‐ APL Kasumi‐1 cells, showing the t (8;21) chromosomal rearrangement, which is prevalent in AML and correlated with a relatively low survival. We demonstrated that the PU .1‐mediated contribution of the 2 miR‐29b precursors is cell‐related and almost completely dependent on adequate levels of Vav1. Nuclear PU .1/Vav1 association accompanies the transcription of miR‐29b but, at variance with the APL ‐derived NB 4 cells, in which the protein is required for the association of PU .1 with both mi RNA promoters, Vav1 is part of molecular complexes to the PU .1 consensus site in Kasumi‐1. Our results add new information on the transcriptional machinery that regulates miR‐29b expression in AML ‐derived cells and may help in identifying drugs useful in upmodulation of this mi RNA in pre‐treatment of patients with non‐ APL leukaemia who can take advantage from hypomethylating agent‐based therapies.