High-Risk Myeloma Is Associated with Global Elevation of Mirnas and Overexpression of EIF2C2/AGO2
High-risk myeloma is associated with global elevation of miRNAs and overexpression of EIF2C2/AGO2 Yiming Zhoua,1, Lijuan Chena,b,1, Bart Barlogiea, Owen Stephensa, Xiaosong Wua, David R. Williamsa, Marie-Astrid Cartrona, Frits van Rheea, Bijay Naira, Sarah Waheeda, Mauricio Pineda-Romana, Yazan Alsayeda, Elias Anaissiea, and John D. Shaughnessy, Jr.a,2 aDonna D. and Donald M. Lambert Laboratory for Myeloma Genetics, Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR 72205; and bDepartment of Hematology, First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, 210029,China Edited* by Carlo M. Croce, Ohio State University, Columbus, OH, and approved March 17, 2010 (received for review July 30, 2009) MicroRNAs (miRNAs) are noncoding RNAs that regulate global gene liferation in MM cell lines, and Lionetti et al. (14) identified 16 expression. miRNAs often act synergistically to repress target genes, miRNAs sensitive to DNA copy number. and their dysregulation can contribute to the initiation and pro- To further investigate the potential involvement of miRNA gression of a variety of cancers. The clinical relationship between in MM, we performed integrative analyses of both miRNA global expression of miRNA and mRNA in cancer has not been expression profiles and protein-coding gene expression profiles studied in detail. We used whole-genome microarray analyses of (GEPs) of myeloma cells from newly diagnosed patients. Global CD138-enriched plasma cells from 52 newly diagnosed cases of increases in miRNA expression were seen in cases with high-risk multiple myeloma to correlate miRNA expression profiles with a MM, which sharply contrasts with discriminate expression validated mRNA-based risk stratification score, proliferation index, changes of only selected miRNAs that are seen in other cancers and predefined gene sets.
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