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MicroRNA 203 expression in keratinocytes is dependent on regulation of p53 levels by E6.
- Source :
-
Journal of virology [J Virol] 2010 Oct; Vol. 84 (20), pp. 10644-52. Date of Electronic Publication: 2010 Aug 11. - Publication Year :
- 2010
-
Abstract
- A screen of microRNA (miRNA) expression following differentiation in human foreskin keratinocytes (HFKs) identified changes in several miRNAs, including miRNA 203 (miR-203), which has previously been shown to play an important role in epithelial cell biology by regulating p63 levels. We investigated how expression of human papillomavirus type 16 (HPV16) oncoproteins E6 and E7 affected miR-203 expression during proliferation and differentiation of HFKs. We demonstrated that miR-203 expression is reduced in HFKs where p53 function is compromised, either by the viral oncoprotein E6 or by knockout of p53 using short hairpin RNAs (p53i). We show that the induction of miR-203 observed during calcium-induced differentiation of HFKs is significantly reduced in HFKs expressing E6 and in p53i HFKs. Induction of miR-203 in response to DNA damage is also reduced in the absence of p53. We report that proliferation of HFKs is dependent on the level of miR-203 expression and that overexpression of miR-203 can reduce overproliferation in E6/E7-expressing and p53i HFKs. In summary, these results indicate that expression of miR-203 is dependent on p53, which may explain how expression of HPV16 E6 can disrupt the balance between proliferation and differentiation, as well as the response to DNA damage, in keratinocytes.
- Subjects :
- Base Sequence
Cell Differentiation
Cell Proliferation
Cells, Cultured
DNA Damage
DNA Primers genetics
Gene Expression
Gene Knockdown Techniques
Host-Pathogen Interactions genetics
Host-Pathogen Interactions physiology
Human papillomavirus 16 genetics
Humans
Keratinocytes pathology
MicroRNAs antagonists & inhibitors
MicroRNAs metabolism
Oncogene Proteins, Viral genetics
Papillomavirus E7 Proteins genetics
Papillomavirus E7 Proteins metabolism
Repressor Proteins genetics
Tumor Suppressor Protein p53 antagonists & inhibitors
Tumor Suppressor Protein p53 genetics
Human papillomavirus 16 pathogenicity
Human papillomavirus 16 physiology
Keratinocytes metabolism
Keratinocytes virology
MicroRNAs genetics
Oncogene Proteins, Viral metabolism
Repressor Proteins metabolism
Tumor Suppressor Protein p53 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1098-5514
- Volume :
- 84
- Issue :
- 20
- Database :
- MEDLINE
- Journal :
- Journal of virology
- Publication Type :
- Academic Journal
- Accession number :
- 20702634
- Full Text :
- https://doi.org/10.1128/JVI.00703-10