Unknown,Transcriptomics,Genomics,Proteomics

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Coordinated regulation of cell cycle transcripts by p53-inducible microRNAs, miR -192 and -215

ABSTRACT: 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. 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

ORGANISM(S): Homo sapiens

SUBMITTER: Aimee Jackson

PROVIDER: E-GEOD-13105 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Coordinated regulation of cell cycle transcripts by p53-Inducible microRNAs, miR-192 and miR-215.

Georges Sara A SA Biery Matthew C MC Kim Soo-Yeon SY Schelter Janell M JM Guo Jane J Chang Aaron N AN Jackson Aimee L AL Carleton Michael O MO Linsley Peter S PS Cleary Michele A MA Chau B Nelson BN

Cancer research 20081201 24

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 G(1) 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 c ...[more]

PMID: 19074876

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Dataset Information

Coordinated regulation of cell cycle transcripts by p53-inducible microRNAs, miR -192 and -215

Publications

Coordinated regulation of cell cycle transcripts by p53-Inducible microRNAs, miR-192 and miR-215.

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