{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Sampath D"],"funding":["NCI NIH HHS"],"pagination":["1162-72"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC3277352"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["119(5)"],"pubmed_abstract":["Chronic lymphocytic leukemia (CLL) demonstrates a global down-regulation of miR-15a and miR-16 and a selective silencing of the related miR-29b in aggressive disease. Deletions in chromosome 13 [del(13q14)] partially account for the loss of expression of miR-15a and miR-16, but the mechanisms by which miR-29b becomes silenced is unknown. In the present study, we show that the histone deacetylases (HDACs) are overexpressed in CLL and mediate the epigenetic silencing of miR-15a, miR-16, and miR-29b. HDAC inhibition triggered the accumulation of the transcriptionally activating chromatin modification H3K4me2 and restored the expression of miR-15a, miR-16, and miR-29b in approximately 35% of samples. Ectopic expression of miR-15a and miR-16 and HDAC inhibition-induced expression of miR-15a, miR-16, or miR-29b in primary CLL cells was associated with declines in the levels of Mcl-1, but not Bcl-2, mitochondrial dysfunction, and induction of cell death. Therefore, our results show that HDACs aberrantly silence the expression of the critical tumor suppressors miR-15a, miR-16, and miR-29b in CLL. Deacetylase inhibition may be a therapeutic strategy that restores the expression of these miRs to antagonize Mcl-1, an important survival protein in these cells. Consequently, CLL patients who exhibit such epigenetic silencing may benefit from HDAC inhibitor-based therapy."],"journal":["Blood"],"pubmed_title":["Histone deacetylases mediate the silencing of miR-15a, miR-16, and miR-29b in chronic lymphocytic leukemia."],"pmcid":["PMC3277352"],"funding_grant_id":["P01 CA081534","CA81534","K24 CA160777"],"pubmed_authors":["Vasan K","Sulda M","Puduvalli VK","Liu C","Keating MJ","Wierda WG","Sampath D"],"additional_accession":[]},"is_claimable":false,"name":"Histone deacetylases mediate the silencing of miR-15a, miR-16, and miR-29b in chronic lymphocytic leukemia.","description":"Chronic lymphocytic leukemia (CLL) demonstrates a global down-regulation of miR-15a and miR-16 and a selective silencing of the related miR-29b in aggressive disease. Deletions in chromosome 13 [del(13q14)] partially account for the loss of expression of miR-15a and miR-16, but the mechanisms by which miR-29b becomes silenced is unknown. In the present study, we show that the histone deacetylases (HDACs) are overexpressed in CLL and mediate the epigenetic silencing of miR-15a, miR-16, and miR-29b. HDAC inhibition triggered the accumulation of the transcriptionally activating chromatin modification H3K4me2 and restored the expression of miR-15a, miR-16, and miR-29b in approximately 35% of samples. Ectopic expression of miR-15a and miR-16 and HDAC inhibition-induced expression of miR-15a, miR-16, or miR-29b in primary CLL cells was associated with declines in the levels of Mcl-1, but not Bcl-2, mitochondrial dysfunction, and induction of cell death. Therefore, our results show that HDACs aberrantly silence the expression of the critical tumor suppressors miR-15a, miR-16, and miR-29b in CLL. Deacetylase inhibition may be a therapeutic strategy that restores the expression of these miRs to antagonize Mcl-1, an important survival protein in these cells. Consequently, CLL patients who exhibit such epigenetic silencing may benefit from HDAC inhibitor-based therapy.","dates":{"release":"2012-01-01T00:00:00Z","publication":"2012 Feb","modification":"2025-04-22T06:58:47.976Z","creation":"2019-03-27T00:49:01Z"},"accession":"S-EPMC3277352","cross_references":{"pubmed":["22096249"],"doi":["10.1182/blood-2011-05-351510"]}}