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E-GEOD-55246 - Inactivation of the exosome ribonuclease DIS3 triggers the pluripotency factor LIN28B, repressing let-7 miRNAs and unleashing MYC and RAS

Released on 12 June 2015, last updated on 21 June 2015
Homo sapiens
Samples (8)
Array (1)
Protocols (8)
Somatic mutations affecting DIS3, the catalytic component of the RNA exosome, have been found in up to 18% of patients affected by the hematological cancer multiple myeloma. Here we show that DIS3 targets and degrades the pluripotency factor LIN28B. In cancer cells, DIS3 inactivation leads to enhanced LIN28B expression, thus disrupting the let-7 miRNAs tumor suppressor network and ultimately increasing protein levels of crucial oncogenes such as MYC and RAS. DIS3 represents the catalytic component of the exosome. The exosome is required for cell viability and targets several RNA species, including pre-mRNAs, pre-tRNAs, pre-rRNAs, snRNAs and snoRNAs. To gain insight on the macular wiring underlying DIS3 activity in mammalian cells, we comprehensively evaluated expression profiles, including miRNAs, in various cell lines, upon DIS3 knockdown. This series of microarray experiments contains the miRNA expression profiles of independent replicates of RPMI-8226, KMS12-BM multiple myeloma cell lines and HEK-293T cells, knocked-down with a scrambled or hDIS3 sh4 and collected 72 hours after infection. 500 nanograms of total RNA were processed using the FlashTag labeling kit, which uses a tailing reaction followed by ligation of the biotinylated signal molecule to the target RNA sample. The labelled RNA was then hybridized to Affymetrix GeneChip® microRNA arrays v1.0, following the Affymetrix manufacturer's instructions.
Experiment type
transcription profiling by array 
Antonino Neri <>, Dejan Lazarevic, Erica C Giuliani, Federico Lazzaro, Giovanna Musco, Giovanni Tonon, Katia Todoerti, Malgorzata A Chudzik, Marco Muzi-Falconi, Silvia Pivetti, Simona Segalla, Stefano Biffo, Viviana Volta
The ribonuclease DIS3 promotes let-7 miRNA maturation by degrading the pluripotency factor LIN28B mRNA. Segalla S, Pivetti S, Todoerti K, Chudzik MA, Giuliani EC, Lazzaro F, Volta V, Lazarevic D, Musco G, Muzi-Falconi M, Neri A, Biffo S, Tonon G.
Investigation descriptionE-GEOD-55246.idf.txt
Sample and data relationshipE-GEOD-55246.sdrf.txt
Raw data (1)
Processed data (1)
Array designA-GEOD-8786.adf.txt