biostudies-literatureZhou YNCI NIH HHS7904-9https://www.ebi.ac.uk/biostudies/studies/S-EPMC2867889biostudies-literatureUnknown107(17)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 iProceedings of the National Academy of Sciences of the United States of AmericaHigh-risk myeloma is associated with global elevation of miRNAs and overexpression of EIF2C2/AGO2.PMC2867889CA55819P01 CA055819Stephens OWaheed SWilliams DRBarlogie BAnaissie EChen LZhou YPineda-Roman MShaughnessy JDAlsayed YCartron MANair Bvan Rhee FWu XfalseHigh-risk myeloma is associated with global elevation of miRNAs and overexpression of EIF2C2/AGO2.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 i2010-01-01T00:00:00Z2010 Apr2026-05-05T06:16:56.432Z2026-04-07T21:24:35.736ZS-EPMC28678892038581810.1073/pnas.0908441107