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• W2007002248 endingPage "e20038" @default.
• W2007002248 startingPage "e20038" @default.
• W2007002248 abstract "CDK5R1 encodes p35, a specific activator of the serine/threonine kinase CDK5, which plays crucial roles in CNS development and maintenance. CDK5 activity strongly depends on p35 levels and p35/CDK5 misregulation is deleterious for correct CNS function, suggesting that a tightly controlled regulation of CDK5R1 expression is needed for proper CDK5 activity. Accordingly, CDK5R1 expression was demonstrated to be controlled at both transcriptional and post-transcriptional levels, but a possible regulation through microRNAs (miRNAs) has never been investigated. We predicted, within the large CDK5R1 3'UTR several miRNA target sites. Among them, we selected for functional studies miR-103 and miR-107, whose expression has shown a strong inverse correlation with p35 levels in different cell lines. A significant reduction of CDK5R1 mRNA and p35 levels was observed after transfection of SK-N-BE neuroblastoma cells with the miR-103 or miR-107 precursor (pre-miR-103 or pre-miR-107). Conversely, p35 levels significantly increased following transfection of the corresponding antagonists (anti-miR-103 or anti-miR-107). Moreover, the level of CDK5R1 transcript shifts from the polysomal to the subpolysomal mRNA fraction after transfection with pre-miR-107 and, conversely, from the subpolysomal to the polysolmal mRNA fraction after transfection with anti-miR-107, suggesting a direct action on translation efficiency. We demonstrate, by means of luciferase assays, that miR-103 and miR-107 are able to directly interact with the CDK5R1 3'-UTR, in correspondence of a specific target site. Finally, miR-103 and miR-107 overexpression, as well as CDK5R1 silencing, caused a reduction in SK-N-BE migration ability, indicating that these miRNAs affect neuronal migration by modulating CDK5R1 expression. These findings indicate that miR-103 and miR-107 regulate CDK5R1 expression, allowing us to hypothesize that a miRNA-mediated mechanism may influence CDK5 activity and the associated molecular pathways." @default.
• W2007002248 created "2016-06-24" @default.
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• W2007002248 date "2011-05-23" @default.
• W2007002248 modified "2023-10-06" @default.
• W2007002248 title "The Role of miR-103 and miR-107 in Regulation of CDK5R1 Expression and in Cellular Migration" @default.
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• W2007002248 doi "https://doi.org/10.1371/journal.pone.0020038" @default.
• W2007002248 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3100319" @default.
• W2007002248 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/21625387" @default.
• W2007002248 hasPublicationYear "2011" @default.
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