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Series GSE39991 Query DataSets for GSE39991
Status Public on Aug 08, 2013
Title Knockdown of Hnrnpa0, a del(5q) Gene, Alters Myeloid Cell Fate in Murine Cells through Regulation of AU-rich Transcripts
Organism Homo sapiens
Experiment type Expression profiling by array
Summary The post-transcriptional control of mRNA stability plays a critical role in numerous biological functions, including the immune response, cell cycle regulation and DNA damage response. HNRNPA0, which encodes an RNA-binding protein shown to regulate transcript stability via binding to the AU-rich elements (AREs) of mRNAs, is located within the commonly deleted segment of 5q31.2 in therapy-related myeloid neoplasms (t-MNs) with a del(5q). We hypothesized that loss of HNRNPA0 leads to alterations in hematopoietic differentiation due to changes in the expression of its target AU-rich transcripts. Using RNAi interference to model Hnrnpa0 loss in primary murine cells and an experimental cell system, we found that reduced Hnrnpa0 expression leads to a shift from monocytic towards granulocytic differentiation. Microarray-based global expression profiling revealed that Hnrnpa0 knockdown disproportionally impacts ARE-containing transcripts and alters expression of myeloid specification genes. The biological importance of ARE-containing genes in myeloid neoplasms is further supported by changes in gene expression of ARE-mRNAs in t-MN del(5q) patients, predicted by pathway analysis to activate tumor growth. Together, our findings suggest that alterations in ARE-containing genes can positively regulate the cellular proliferation of del(5q) cells and implicate haploinsufficiency of HNRNPA0 as one of the key initiation mutations in the pathogenesis of t-MN.
 
Overall design Gene expression profiling was performed on 38 single t-MN tumor samples. No control or reference samples were included.
 
Contributor(s) Young DJ, Stoddart A, Nakitandwe J, Chen S, Qian Z, Downing JR, Le Beau MM
Citation(s) 24532040
Submission date Aug 08, 2012
Last update date Apr 20, 2018
Contact name Shann-Ching Chen
E-mail(s) Shann-Ching.Chen@stjude.org
Organization name St. Jude Children's Research Hospital
Department Pathology
Street address 262 Danny Thomas Place
City Memphis
State/province TN
ZIP/Postal code 38105
Country USA
 
Platforms (1)
GPL13158 [HT_HG-U133_Plus_PM] Affymetrix HT HG-U133+ PM Array Plate
Samples (38)
GSM983011 tAML patient sample SJTAML002
GSM983012 tAML patient sample SJTAML005
GSM983013 tAML patient sample SJTAML008
Relations
BioProject PRJNA172212

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Supplementary file Size Download File type/resource
GSE39991_RAW.tar 72.8 Mb (http)(custom) TAR (of CEL)
Processed data included within Sample table

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