Please use this identifier to cite or link to this item: https://doi.org/10.18632/oncotarget.4769
Title: Genome-wide pharmacologic unmasking identifies tumor suppressive microRNAs in multiple myeloma
Authors: Bi, C
Chung, T.-H 
Huang, G 
Zhou, J 
Yan, J 
Ahmann, G.J
Fonseca, R
Chng, W.J 
Keywords: microRNA
microRNA 125a 3p
microRNA 135a
microRNA 155
microRNA 188 5p
microRNA 198
microRNA 200c
microRNA 483 5p
microRNA 630
microRNA 663
unclassified drug
DNA methyltransferase
enzyme inhibitor
microRNA
tumor marker
Article
cancer survival
cell proliferation
cell viability
colony formation
controlled study
CpG island
DNA methylation
epigenetics
gene expression
human
human cell
migration inhibition
multiple myeloma
RNA analysis
antagonists and inhibitors
biology
cell motion
DNA microarray
drug effects
gene expression profiling
gene expression regulation
gene silencing
genetic predisposition
genetics
genome-wide association study
metabolism
mortality
multiple myeloma
pathology
phenotype
procedures
proportional hazards model
tumor cell line
Biomarkers, Tumor
Cell Line, Tumor
Cell Movement
Cell Proliferation
Computational Biology
DNA Methylation
DNA Modification Methylases
Enzyme Inhibitors
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Gene Silencing
Genetic Predisposition to Disease
Genome-Wide Association Study
Humans
MicroRNAs
Multiple Myeloma
Oligonucleotide Array Sequence Analysis
Phenotype
Proportional Hazards Models
Issue Date: 2015
Citation: Bi, C, Chung, T.-H, Huang, G, Zhou, J, Yan, J, Ahmann, G.J, Fonseca, R, Chng, W.J (2015). Genome-wide pharmacologic unmasking identifies tumor suppressive microRNAs in multiple myeloma. Oncotarget 6 (28) : 26508-26518. ScholarBank@NUS Repository. https://doi.org/10.18632/oncotarget.4769
Abstract: Epigenetic alterations have emerged as an important cause of microRNA (miRNA) deregulation. In Multiple Myeloma (MM), a few tumor suppressive miRNAs silenced by DNA hypermethylation have been reported, but so far there are few systemic investigations on epigenetically silenced miRNAs. We conducted genomewide screening for tumor suppressive miRNAs epigenetically silenced in MM. Four Human MM Cell lines were treated with demethylating agent 5'azacytidine (5'aza). Consistently upregulated miRNAs include miR-155, miR-198, miR-135a*, miR-200c, miR-125a-3p, miR-188-5p, miR-483-5p, miR-663, and miR-630. Methylation array analysis revealed increased methylation at or near miRNA-associated CpG islands in MM patients. Ectopic restoration of miR-155, miR-198, miR-135a*, miR-200c, miR-663 and miR-483-5p significantly repressed MM cell proliferation, migration and colony formation. Furthermore, we derived a 33-gene signature from predicted miRNA target genes that were also upregulated in MM patients and associated with patient survival in three independent myeloma datasets. In summary, we have revealed important, epigenetically silenced tumor suppressive miRNAs by pharmacologic reversal of epigenetic silencing.
Source Title: Oncotarget
URI: https://scholarbank.nus.edu.sg/handle/10635/174136
ISSN: 19492553
DOI: 10.18632/oncotarget.4769
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