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Identification of genes potentially regulated by human polynucleotide phosphorylase (hPNPase old-35) using melanoma as a model
- Source :
- PLoS ONE, Vol 8, Iss 10, p e76284 (2013), PLoS ONE
- Publication Year :
- 2013
- Publisher :
- Public Library of Science (PLoS), 2013.
-
Abstract
- Human Polynucleotide Phosphorylase (hPNPase(old-35) or PNPT1) is an evolutionarily conserved 3'→ 5' exoribonuclease implicated in the regulation of numerous physiological processes including maintenance of mitochondrial homeostasis, mtRNA import and aging-associated inflammation. From an RNase perspective, little is known about the RNA or miRNA species it targets for degradation or whose expression it regulates; except for c-myc and miR-221. To further elucidate the functional implications of hPNPase(old-35) in cellular physiology, we knocked-down and overexpressed hPNPase(old-35) in human melanoma cells and performed gene expression analyses to identify differentially expressed transcripts. Ingenuity Pathway Analysis indicated that knockdown of hPNPase(old-35) resulted in significant gene expression changes associated with mitochondrial dysfunction and cholesterol biosynthesis; whereas overexpression of hPNPase(old-35) caused global changes in cell-cycle related functions. Additionally, comparative gene expression analyses between our hPNPase(old-35) knockdown and overexpression datasets allowed us to identify 77 potential "direct" and 61 potential "indirect" targets of hPNPase(old-35) which formed correlated networks enriched for cell-cycle and wound healing functional association, respectively. These results provide a comprehensive database of genes responsive to hPNPase(old-35) expression levels; along with the identification new potential candidate genes offering fresh insight into cellular pathways regulated by PNPT1 and which may be used in the future for possible therapeutic intervention in mitochondrial- or inflammation-associated disease phenotypes.
- Subjects :
- DNA, Complementary
lcsh:Medicine
Biology
Adenoviridae
03 medical and health sciences
0302 clinical medicine
Cell Line, Tumor
Databases, Genetic
microRNA
Gene expression
Gene Knockdown Techniques
Humans
Polynucleotide phosphorylase
Cloning, Molecular
lcsh:Science
Melanoma
Gene
030304 developmental biology
Genetics
Regulation of gene expression
0303 health sciences
Gene knockdown
Multidisciplinary
lcsh:R
Gene Expression Regulation, Neoplastic
030220 oncology & carcinogenesis
Exoribonucleases
lcsh:Q
DNA microarray
Research Article
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 8
- Issue :
- 10
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....146d3ec223266e47f82e0e2be5ccf934