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Expression data from miR-203 induction in mouse skin

ABSTRACT: We identify numerous miR-203 in vivo targets that are highly enriched for the promotion of cell cycle and cell division. Importantly, individual targets including p63, Skp2 and Msi2 play distinct roles downstream of miR-203 to regulate the cell cycle and long-term proliferation. Together, our findings reveal rapid and widespread impact of miR-203 on the self-renewal program during the epidermal differentiation and provide mechanistic insights for the potent role of miR-203 where coordinated repression of multiple targets is required for the function of this miRNA. We used microarrays to measure transcriptome changes upon miR-203's induction in mouse skin and identified new targets of miR-203.

ORGANISM(S): Mus musculus

PROVIDER: GSE45121 | GEO | 2013/03/14

SECONDARY ACCESSION(S): PRJNA192930

REPOSITORIES: GEO

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Expression data from miR-203 induction in mouse skin

Project description:We identify numerous miR-203 in vivo targets that are highly enriched for the promotion of cell cycle and cell division. Importantly, individual targets including p63, Skp2 and Msi2 play distinct roles downstream of miR-203 to regulate the cell cycle and long-term proliferation. Together, our findings reveal rapid and widespread impact of miR-203 on the self-renewal program during the epidermal differentiation and provide mechanistic insights for the potent role of miR-203 where coordinated repression of multiple targets is required for the function of this miRNA. We used microarrays to measure transcriptome changes upon miR-203's induction in mouse skin and identified new targets of miR-203. We use two pairs of biological duplicates to perform the microarray analysis from the epidermal samples harvested from K14-rtTA/TRE-miR-203/K14-H2BGFP (DP) and TRE-miR-203/K14-H2BGFP (SP) littermates at P4, 24h after the Dox injection.

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Project description:The colonization of distant organs by metastatic carcinoma cells underpins most human cancer-related deaths, including those from head and neck squamous cell carcinoma (HNSCC). We report that miR-203, a miRNA that promotes keratinocyte differentiation, is necessary and sufficient to inhibit multiple post-extravasation events during HNSCC lung metastasis, including initial survival/engraftment, escape from metastatic dormancy, and overt colonization in vivo. Restoration of miR-203 expression in established lung metastases reduces overall metastatic burden. Instead of promoting differentiation, miR-203 controls lung metastasis through direct targeting of genes involved in cytoskeletal dynamics (LASP1), ECM remodeling (SPARC), and cell metabolism (NUAK1). Expression of miR-203 and its downstream targets correlates with HNSCC overall survival outcomes, suggesting the therapeutic potential of targeting this signaling axis.

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