title: Silencing of the WFS1 gene in HEK cells induces pathways related to neurodegeneration and mitochondrial damage.
abstract: The gene WFS1 encodes a protein with unknown function although its functional deficiency causes different neuropsychiatric and neuroendocrine syndromes. In the present study, we aimed to find the functional networks influenced by the time-dependent silencing of WFS1 in HEK cells. We performed whole genome gene expression profiling (Human Gene 1.0 ST Arrays) in HEK cells 24, 48, 72, and 96 h after transfection with three different WFS1 siRNAs. To verify silencing we performed quantitative RT-PCR and Western blot analysis. Analysis was conducted in two ways. First we analyzed the overall effect of the siRNA treatment on the gene expression profile. As a next step we performed time-course analysis separately for different siRNAs and combined for all siRNAs. Quantitative RT-PCR and Western blot analysis confirmed clear silencing of the expression of WFS1 after 48 h. Significant (FDR value<10%) changes in the expression of 11 genes was identified with most of these genes being related to the mitochondrial dysfunction and apoptosis. Time-course analysis confirmed significant correlations between WFS1 silencing and changes in the expression profiles of several genes. The pathways that were influenced significantly by WFS1 silencing were related to mitochondrial damage and neurodegenerative diseases. Our findings suggest a role of WFS1 gene in cell survival and its involvement in degenerative diseases.
authors: Department of Physiology, University of Tartu, Tartu, Estonia. sulev.koks@ut.ee
authors: Sulev
authors: S
authors: Kõks
authors: Rupert W
authors: RW
authors: Overall
authors: Marilin
authors: M
authors: Ivask
authors: Ursel
authors: U
authors: Soomets
authors: Mithu
authors: M
authors: Guha
authors: Eero
authors: E
authors: Vasar
authors: Cathy
authors: C
authors: Fernandes
authors: Leo C
authors: LC
authors: Schalkwyk
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D020869:Gene Expression Profiling; D020868:Gene Silencing; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000378:metabolism* / Q000473:pathology*; D008962:Models, Theoretical; D019636:Neurodegenerative Diseases / Q000378:metabolism* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014929:Wolfram Syndrome / Q000378:metabolism
chemical_list: D008565:Membrane Proteins; C114987:wolframin protein