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| Status |
Public on Dec 07, 2008 |
| Title |
Coordinated regulation of cell cycle transcripts by p53-inducible microRNAs, miR -192 and -215 |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Cell cycle arrest in response to DNA damage is an important anti-tumorigenic mechanism. microRNAs (miRNAs) were shown recently 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 microRNA families operate in the p53 network. Furthermore, we define a downstream gene expression signature for miR-192/215 expression that 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 demonstrating a role for miR-192/215 in cell proliferation combined with recent observations that these miRNAs are under-expressed in primary cancers support the idea that miR-192 and miR-215 function as tumor-suppressors.
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| Overall design |
Description: Transfection of siRNA luc, miR-192 or miR-215 into HCT116 Dicerex5, compared to mock-transfected cells, with mRNA expression profiled at 10h and 24h post-transfection.
Species: Human
Tissue: HCT116 Dicerex5 cell line (tissue of origin = human colorectal carcinoma); this cell line is hypomorphic for Dicer gene function.
Dye-swap: no
Negative control: siRNA luc
Replicates per each timepoint: no
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| Contributor(s) |
Georges SA, Biery MC, Kim S, Schelter JM, Guo J, Chang AN, Jackson AL, Carleton MO, Linsley PS, Cleary MA, Chau N |
| Citation(s) |
19074876 |
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| Submission date |
Oct 07, 2008 |
| Last update date |
Mar 20, 2012 |
| Contact name |
Sara Georges |
| E-mail(s) |
[email protected]
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| Phone |
(206) 802-6305
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| Fax |
(206) 802-7399
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| Organization name |
Rosetta Inpharmatics, LLC
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| Street address |
401 Terry Ave N
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| City |
Seattle |
| State/province |
WA |
| ZIP/Postal code |
98109 |
| Country |
USA |
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| Platforms (1) |
| GPL4372 |
Rosetta/Merck Human 44k 1.1 microarray |
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| Samples (6)
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| GSM328286 |
HCT116 Dicer-/- #2, mock vs. HCT116 Dicer-/- #2, luc, 25nM, 24hr |
| GSM328287 |
HCT116 Dicer-/- #2, mock vs. HCT116 Dicer-/- #2, miR-192, 25nM, 24hr |
| GSM328288 |
HCT116 Dicer-/- #2, mock vs. HCT116 Dicer-/- #2, miR-215, 25nM, 24hr |
| GSM328289 |
HCT116 Dicer-/- #2, mock vs. HCT116 Dicer-/- #2, luc, 25nM, 10hr |
| GSM328290 |
HCT116 Dicer-/- #2, mock vs. HCT116 Dicer-/- #2, miR-192, 25nM, 10hr |
| GSM328291 |
HCT116 Dicer-/- #2, mock vs. HCT116 Dicer-/- #2, miR-215, 25nM, 10hr |
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| Relations |
| BioProject |
PRJNA109937 |
| Supplementary data files not provided |
| Processed data included within Sample table |
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