Interleukin-8 is regulated by miR-203 at the posttranscriptional level in primary human keratinocytes.

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Interleukin-8 is regulated by miR-203 at the posttranscriptional level in primary human keratinocytes.

Wei, Tianling (author)

Xu, Ning (author): Karolinska Institutet

Meisgen, Florian (author): Karolinska Institutet

Ståhle, Mona (author): Karolinska Institutet

Sonkoly, Enikö (author): Karolinska Institutet

Pivarcsi, Andor (author): Karolinska Institutet

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(creator_code:org_t)

2013
2013
English.
In: EJD. European journal of dermatology. - 1167-1122 .- 1952-4013.

Related links:: https://urn.kb.se/re...; show more...; http://kipublication...; show less...

Journal article (peer-reviewed)

Abstract Subject headings

Background: MicroRNAs are important posttranscriptional regulators of gene expression. MiR-203 is a miRNA preferentially expressed in the skin, and an important regulator of keratinocyte differentiation. MiR-203 has been implicated in skin diseases, in particular in psoriasis in which it is overexpressed, and in basal cell carcinoma where it acts as a tumor suppressor miRNA. Objectives: To identify novel targets for miR-203 that may be relevant in skin physiology and diseases. Materials & Methods: Bioinformatics was used to identify putative miR-203 targets among genes expressed in keratinocytes. Interleukin-8 (IL-8) gene expression and concentration in keratinocyte medium was measured by quantitative real-time PCR and ELISA, respectively. For miRNA overexpression, resting or TNF-α-treated primary human keratinocytes were transfected with synthetic precursor of miR-203, or scramble miRNA precursors using Lipofectamine 2000. 3'UTR luciferase reporter experiments were performed to prove the direct miRNA:mRNA interaction. Site-specific mutagenesis was used to mutate the predicted miR-203 binding sites in the 3'UTR of IL-8 gene. Results: Bioinformatic analysis indentified two putative miR-203 binding sites in the 3'UTR of IL-8. MiR-203 suppressed IL-8 mRNA and protein expression in primary human keratinocytes both under resting conditions and after TNF-α treatment. Overexpression of miR-203 suppressed the luciferase activity of a reporter gene fused with the IL-8 3'UTR. The suppressive effect was abolished when the predicted binding sites of miR-203 on IL-8 3'UTR were mutated. Conclusion: We identify IL-8 as a novel target of miR-203 for posttranscriptional suppression. These findings may have relevance in diseases in which miR-203 and IL-8 expression are deregulated.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Dermatologi och venereologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Dermatology and Venereal Diseases (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)

Keyword

IL-8
chemokine
cytokines
microRNAs
non-melanoma skin cancer
psoriasis
skin

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ref (subject category)
art (subject category)

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By the author/editor: Wei, Tianling; Xu, Ning; Meisgen, Florian; Ståhle, Mona; Sonkoly, Enikö; Pivarcsi, Andor

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Immunology in th ...

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Dermatology and ...

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Cell and Molecul ...

Articles in the publication: EJD. European jo ...

By the university: Uppsala University; Karolinska Institutet

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