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| Status |
Public on Jun 12, 2015 |
| Title |
Inactivation of the exosome ribonuclease DIS3 triggers the pluripotency factor LIN28B, repressing let-7 miRNAs and unleashing MYC and RAS. |
| Platform organism |
synthetic construct |
| Sample organism |
Homo sapiens |
| Experiment type |
Non-coding RNA profiling by array
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| Summary |
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.
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| Overall design |
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.
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| Contributor(s) |
Segalla S, Pivetti S, Giuliani EC, Chudzik MA, Lazzaro F, Volta V, Todoerti K, Lazarevic D, Musco G, Muzi-Falconi M, Neri A, Biffo S, Tonon G |
| Citation(s) |
25925570 |
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| Submission date |
Feb 21, 2014 |
| Last update date |
May 02, 2017 |
| Contact name |
Luca Agnelli |
| E-mail(s) |
luca.agnelli@istitutotumori.mi.it, luca.agnelli@gmail.com
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| Phone |
+390223903581
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| Organization name |
IRCCS Istituto Nazionale dei Tumori
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| Department |
Department of Advanced Diagnostics
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| Street address |
Venezian 1
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| City |
MILAN |
| ZIP/Postal code |
20133 |
| Country |
Italy |
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| Platforms (1) |
| GPL8786 |
[miRNA-1] Affymetrix Multispecies miRNA-1 Array |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA238992 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE55246_RAW.tar |
1.3 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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