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Series GSE53482 Query DataSets for GSE53482
Status Public on Oct 01, 2014
Title Integrative Analysis of Gene and miRNA expression profiles in Primary Myelofibrosis CD34+ cells
Platform organisms Homo sapiens; synthetic construct
Sample organism Homo sapiens
Experiment type Expression profiling by array
Non-coding RNA profiling by array
Summary Ph-negative myeloproliferative neoplasms (MPNs) are characterized by many somatic mutations which have already been shown useful in the prognostic assessment of MPN patients. Moreover, aberrant microRNA (miRNA) expression seems to add to the molecular complexity of MPNs, as specific miRNA signatures capable of discriminating MPN cells from those of normal donors were previously reported. In order to have a comprehensive picture of miRNA deregulation and its relationship with differential gene expression in primary myelofibrosis (PMF) cells, we obtained gene- (GEP) and miRNA expression profiles (miEP) of CD34+ cells from 31 healthy donors and 42 PMF patients using Affymetrix technology (HG-U219 and miRNA 2.0 arrays). Differentially expressed genes (DEG) and miRNAs (DEM) were sorted out by means of Partek Genomic Suite vs 6.6. Since each miRNA can target many mRNAs while a single mRNA can be targeted by multiple miRNAs, we performed Integrative Analysis (IA) by means of Ingenuity Pathway Analysis (IPA) to untangle this combinatorial complexity. In particular, IPA points out DEM-DEG pairs among experimentally validated interactions from TarBase, miRecords and Ingenuity Expert Findings as well as predicted microRNA-mRNA interactions from TargetScan. IPA microRNA Target Filter was then employed to select only the DEM-DEG pairs showing an anti-correlated expression pattern and to build regulatory networks. Finally, 3'UTR luciferase reporter assays were performed to validate IPA predicted miRNA-mRNA interactions.
This study allowed the identification of different networks possibly involved in PMF onset and progression, highlighting an aberrant cross-regulation in miRNA-targets involved in malignant hematopoiesis. Furthermore, Integrative analysis was proved a powerful tool to unravel miRNA-mRNA interactions in functional networks, shedding light on the potential contribution of miRNAs to PMF pathogenesis.
 
Overall design Gene expression profile (GEP) and miRNA expression profile (miEP) were performed starting from the same totalRNA of CD34+ cells from 42 PMF patients and 31 healthy donors (n=16 PB CD34+, n=15 BM CD34+) (1 replicate for each sample). In particular, GEP and miEP were performed on 23 PMF patients carrying the mutation JAK2V617F and 19 wild-type samples.
 
Contributor(s) Norfo R, Zini R, Pennucci V, Guglielmelli P, Fanelli T, Bogani C, Bianchi E, Salati S, Ruberti S, Prudente Z, Sacchi G, Rontauroli S, Pietra D, Salmoiraghi S, Bisognin A, Bortoluzzi S, Barosi G, Cazzola M, Rambaldi A, Tagliafico E, Vannucchi AM, Manfredini R
Citation(s) 25097177, 28423484, 26547506
Submission date Dec 18, 2013
Last update date Mar 21, 2019
Contact name Rossella Manfredini
E-mail(s) manfredini.rossella@unimore.it
Phone +390592058065
Organization name Centre for Regenerative Medicine
Department Life Sciences
Street address Via Gottardi 100
City Modena
ZIP/Postal code 41100
Country Italy
 
Platforms (2)
GPL13667 [HG-U219] Affymetrix Human Genome U219 Array
GPL14613 [miRNA-2] Affymetrix Multispecies miRNA-2 Array
Samples (146)
GSM1294399 PB CD34+ cells from PMF patient 4771 (miEP)
GSM1294400 PB CD34+ cells from PMF patient 4831 (miEP)
GSM1294401 PB CD34+ cells from PMF patient 5005 (miEP)
Relations
BioProject PRJNA232279

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE53482_RAW.tar 195.6 Mb (http)(custom) TAR (of CEL)
GSE53482_additional_sample_characteristics.txt.gz 1.2 Kb (ftp)(http) TXT
Processed data included within Sample table
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