Identification of miR-141 as a new regulator of epidermal homeostatis, in cooperation with miR-203
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ABSTRACT:
PROVIDER: PRJNA1099215 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR28628100.fastq.gz | Fastqsanger.gz | |||
| SRR28628101.fastq.gz | Fastqsanger.gz | |||
| SRR28628102.fastq.gz | Fastqsanger.gz | |||
| SRR28628097.fastq.gz | Fastqsanger.gz | |||
| SRR28628098.fastq.gz | Fastqsanger.gz |
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Project description:MicroRNAs, small endogenous non-coding RNAs, are involved in the regulation of epidermal homeostasis. Among them, miR-203 was the most described and expressed in human epidermis, promoting keratinocyte differentiation by repressing genes involved in proliferation. To identify other miRNAs involved in this process, the miRNomes of normal human keratinocytes cultured in monolayer (2D) or in 3D reconstructed skin were compared. Besides miR-203, mR-141 was one of the most expressed miRNAs in 3D culture and was overexpressed in 3D vs 2D condition, i.e. during keratinocyte differentiation. Functional experiments revealed that, mostly expressed in the basal layer, miR-141 decreased keratinocyte proliferation and clonogenicity while promoting their differentiation. Target prediction algorithm coupled with transcriptomic data of keratinocytes overexpressing miR-141, as well as 3’UTR luciferase assays enabled to evidence CCND2 mRNA as a direct target of miR-141, leading to its down regulation by miR-141 overexpression. Finally, CCND2 silencing decreased keratinocyte proliferation and induced their differentiation, revealing that miR-141 action was mediated by CCND2. MiR-141 features were also compared with miR-203 in parallel experiments. Although miR-141 displayed similar functions to the ones of miR-203, it exhibited different localization and targets, suggesting a joint participation of miR-141 and miR-203 to engage and maintain keratinocyte towards differentiation, respectively.
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Project description:Identification of miR-141 as a new regulator of epidermal homeostasis, in cooperation with miR-203
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Project description:To identify putative novel specific targets of miR-141-3p, we overexpressed this miRNAs in primary keratinocytes using a synthetic mimic (pre-miR-141-3p) or a synthetic “negative” control mimic (pre-miR-ctrl). RNA samples were harvested 30 hours post-transfection and 3 independent experiments were carried out.
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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.
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