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Pathway Analysis of Global Gene Expression Changes in rat liver following silencing of c‐met by RNA Interference.
Author(s) -
Paranjpe Shirish,
Tseng George,
Chattopadhyay Ansuman,
Luo Jianhua,
Michalopoulos George K
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1124.1
Subject(s) - biology , gene silencing , gene , gene expression , microarray , microarray analysis techniques , dna microarray , microbiology and biotechnology , small hairpin rna , gene expression profiling , rna interference , cell cycle , rna , genetics
We have reported Cell cycle effects resulting from shRNA mediated inhibition of hepatocyte growth factor and its receptor c‐Met in regenerating rat livers following a partial hepatectomy (Hepatology, 45: 1471–1477). Microarray analysis of shMet and scrambled treated rat livers using Affymetrix U230.2 A chip containing 10,000 expressed sequences indicated abnormal expression of genes associated with cell cycle and apoptosis. Cluster analysis of microarray data was then carried out. Normalization and preprocessing of data from 8 chips was by dChip software. Expression intensities were log transformed and genes with expression level less than 7 or SD smaller than 0.5 were filtered out. Hierarchical clustering of the remaining 4747 genes according to similarity in pattern of gene expression produced 8 clusters. Of the 4747 genes, 805 genes whose expression value was >2 or <–2 compared to the corresponding control group were then analyzed using Ingenuity software. Networks were generated for each time point post PHx for shMet treatment and control group. It was observed that the genes associated with DNA repair, fatty acid metabolism, p38 MAPK pathway, and bile acid biosynthetic pathway were differentially regulated in shMet silenced rats when compared to scrambled treated controls. Suppression of c‐met thus caused profound alterations in multiple signalling pathways.