Coordinated Regulation of Cell Cycle Transcripts by p53-Inducible microRNAs, miR-192 and miR-215
| Autor: | Janell M. Schelter, B. Nelson Chau, Matthew Biery, Aaron N. Chang, Peter S. Linsley, Jane Guo, Soo Yeon Kim, Sara A Georges, Aimee L. Jackson, Michael Carleton, Michele A. Cleary |
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| Rok vydání: | 2008 |
| Předmět: |
G2 Phase
Cancer Research Cell cycle checkpoint Cell Biology Transfection Neoplasms microRNA medicine Humans Gene silencing Gene Silencing RNA Messenger CHEK1 Regulation of gene expression Gene Expression Profiling Cell Cycle G1 Phase DNA Neoplasm Cell cycle Genes p53 HCT116 Cells Up-Regulation Cell biology Gene Expression Regulation Neoplastic Gene expression profiling MicroRNAs medicine.anatomical_structure Oncology Tumor Suppressor Protein p53 Cell Division DNA Damage |
| Zdroj: | Cancer Research. 68:10105-10112 |
| ISSN: | 1538-7445 0008-5472 |
| Popis: | Cell cycle arrest in response to DNA damage is an important antitumorigenic mechanism. MicroRNAs (miRNAs) were recently shown to play key regulatory roles in cell cycle progression. For example, miR-34a is induced in response to p53 activation and mediates G1 arrest by down-regulating multiple cell cycle–related transcripts. Here we show that genotoxic stress promotes the p53-dependent up-regulation of the homologous miRNAs miR-192 and miR-215. Like miR-34a, activation of miR-192/215 induces cell cycle arrest, suggesting that multiple miRNA families operate in the p53 network. Furthermore, we define a downstream gene expression signature for miR-192/215 expression, which includes a number of transcripts that regulate G1 and G2 checkpoints. Of these transcripts, 18 transcripts are direct targets of miR-192/215, and the observed cell cycle arrest likely results from a cooperative effect among the modulations of these genes by the miRNAs. Our results showing a role for miR-192/215 in cell proliferation combined with recent observations that these miRNAs are underexpressed in primary cancers support the idea that miR-192 and miR-215 function as tumor suppressors. [Cancer Res 2008;68(24):10105–12] |
| Databáze: | OpenAIRE |
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