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• W1993469143 abstract "MicroRNAs (miRNAs) are noncoding RNAs that regulate global gene expression. miRNAs often act synergistically to repress target genes, and their dysregulation can contribute to the initiation and progression of a variety of cancers. The clinical relationship between global expression of miRNA and mRNA in cancer has not been studied in detail. We used whole-genome microarray analyses of CD138-enriched plasma cells from 52 newly diagnosed cases of multiple myeloma to correlate miRNA expression profiles with a validated mRNA-based risk stratification score, proliferation index, and predefined gene sets. In stark contrast to mRNAs, we discovered that all tested miRNAs were significantly up-regulated in high-risk disease as defined by a validated 70-gene risk score ( P < 0.01) and proliferation index ( P < 0.05). Increased expression of EIF2C2/AGO2 , a master regulator of the maturation and function of miRNAs and a component of the 70-gene mRNA risk model, is driven by DNA copy number gains in MM. Silencing of AGO2 dramatically decreased viability in MM cell lines. Genome-wide elevated expression of miRNAs in high-risk MM may be secondary to deregulation of AGO2 and the enzyme complexes that regulate miRNA maturation and function." @default.
• W1993469143 created "2016-06-24" @default.
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• W1993469143 date "2010-04-12" @default.
• W1993469143 modified "2023-10-16" @default.
• W1993469143 title "High-risk myeloma is associated with global elevation of miRNAs and overexpression of <i>EIF2C2/AGO2</i>" @default.
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• W1993469143 doi "https://doi.org/10.1073/pnas.0908441107" @default.
• W1993469143 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2867889" @default.
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