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TAp63 regulates oncogenic miR-155 to mediate migration and tumour growth
- Source :
- Oncotarget
- Publication Year :
- 2013
- Publisher :
- Impact Journals LLC, 2013.
-
Abstract
- // Sam Mattiske 1 , Kristen Ho 1 , Jacqueline E. Noll 1 , Paul M. Neilsen 1 , David F. Callen 1 and Rachel J. Suetani 1 1 Cancer Therapeutics Laboratory, Centre for Personalised Cancer Medicine, University of Adelaide, Australia Correspondence: David Callen, email: // Sam Mattiske, email: // Keywords : miR-155, TAp63, ΔNp63, cancer, tumorigenesis, migration Received : July 31, 2013 Accepted : August 29, 2013 Published : August 31, 2013 Abstract miR-155 is an oncogenic microRNA which is upregulated in many solid cancers. The targets of miR-155 are well established , with over 100 confirmed mRNA targets. However, the regulation of miR-155 and the basis of its upregulation in cancer is not well understood. We have previously shown that miR-155 is regulated by p63, and here we investigate the role of the major p63 isoforms TAp63 and ΔNp63 in this regulation. When the TAp63 isoform was knocked down, or exogenously overexpressed, miR-155 levels were elevated in response to TAp63 knockdown or reduced in response to TAp63 overexpression. The ΔNp63 isoform is shown to directly bind to the p63 response element on the miR-155 host gene, and this binding is enriched when TAp63 is knocked down. This could indicate that TAp63 prevents ΔNp63 from binding to the miR-155 host gene. The knockdown of TAp63, and the subsequent elevation of miR-155, enhances migration and tumour growth similar to that seen when directly overexpressing miR-155. The migratory phenotype is abrogated when miR-155 is inhibited, indicating that miR-155 is responsible for the phenotypic effect of TAp63 knockdown.
- Subjects :
- Gene isoform
Response element
Mice, Nude
Breast Neoplasms
Biology
medicine.disease_cause
migration
miR-155
03 medical and health sciences
Mice
0302 clinical medicine
Downregulation and upregulation
Cell Movement
microRNA
Gene Knockdown Techniques
medicine
cancer
Animals
Humans
TAp63
030304 developmental biology
0303 health sciences
Gene knockdown
Mice, Inbred BALB C
Tumor Suppressor Proteins
3. Good health
Up-Regulation
Gene Expression Regulation, Neoplastic
tumorigenesis
MicroRNAs
Oncology
030220 oncology & carcinogenesis
ΔNp63
Cancer research
Heterografts
Female
Carcinogenesis
Research Paper
Transcription Factors
Subjects
Details
- Language :
- English
- ISSN :
- 19492553
- Volume :
- 4
- Issue :
- 11
- Database :
- OpenAIRE
- Journal :
- Oncotarget
- Accession number :
- edsair.doi.dedup.....eee4523a37194e14310470a16b896547