Genome-wide pharmacologic unmasking identifies tumor suppressive microRNAs in multiple myeloma.

摘要: // Chonglei Bi 1,2 , Tae-Hoon Chung 1 Gaofeng Huang Jianbiao Zhou Junli Yan Gregory J. Ahmann 3 Rafael Fonseca and Wee Joo Chng 1,2,4 Experimental Therapeutics, Cancer Science Institute of Singapore, Singapore 2 Department Medicine, Yong Loo Lin School National University Mayo Clinic, Scottsdale, Arizona, USA 4 Hematology-Oncology, Institute, Health System, Correspondence to: Chng, email: Keywords : tumor suppressor, epigenetics, microRNA, myeloma Received April 16, 2015 Accepted June 25, Published July 03, Abstract Epigenetic alterations have emerged as an important cause microRNA (miRNA) deregulation. In Multiple Myeloma (MM), a few suppressive miRNAs silenced by DNA hypermethylation been reported, but so far there are systemic investigations on epigenetically miRNAs. We conducted genome-wide screening for in MM. Four Human MM Cell lines were treated with demethylating agent 5’azacytidine (5’aza). Consistently upregulated include miR-155, miR-198, miR-135a*, miR-200c, miR-125a-3p, miR-188-5p, miR-483-5p, miR-663, miR-630. Methylation array analysis revealed increased methylation at or near miRNA-associated CpG islands patients. Ectopic restoration miR-663 miR-483-5p significantly repressed cell proliferation, migration colony formation. Furthermore, we derived 33-gene signature from predicted miRNA target genes that also patients associated patient survival three independent datasets. summary, important, pharmacologic reversal epigenetic silencing.