Role of miR-506 in ulcerative colitis associated with primary sclerosing cholangitis

Abstract Primary sclerosing cholangitis (PSC) is commonly accompanied by ulcerative colitis (UC). MicroRNA-506 modulates expression of genes which are essential for sphingosine-mediated signaling pathway and intestinal mucosa protection. We investigated whether miR-506 and its target genes are invol...

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Autores principales:	Agnieszka Kempinska-Podhorodecka, Monika Adamowicz, Ewa Ostrycharz, Mateusz Chmielarz, Maciej Wójcicki, Piotr Milkiewicz, Malgorzata Milkiewicz
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ec2d1e2b90ec47b4a63193e5913e629d
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spelling	oai:doaj.org-article:ec2d1e2b90ec47b4a63193e5913e629d2021-12-02T17:16:05ZRole of miR-506 in ulcerative colitis associated with primary sclerosing cholangitis10.1038/s41598-021-89631-42045-2322https://doaj.org/article/ec2d1e2b90ec47b4a63193e5913e629d2021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-89631-4https://doaj.org/toc/2045-2322Abstract Primary sclerosing cholangitis (PSC) is commonly accompanied by ulcerative colitis (UC). MicroRNA-506 modulates expression of genes which are essential for sphingosine-mediated signaling pathway and intestinal mucosa protection. We investigated whether miR-506 and its target genes are involved in phenotypic presentations of colonic inflammation and/or neoplasia. We analyzed serum and colon tissue samples collected from patients with PSC, PSC with concurrent UC (PSC + UC), UC alone, and healthy controls (n = 10 each). MiR-506 was substantially upregulated in ascending colons of PSC and PSC + UC patients, in contrast to sigmoid colons of PSC and UC patients. Upregulation of miR-506 was associated with inhibition of SPHK1, AE2, InsP3R3, and p53. Colonic suppression of miR-506 presented in UC was accompanied by substantially increased DNMT1, SPHK1, and S1P lyase expressions. A functional in vitro analysis in Caco-2 cells showed that the induction of miR-506 activity by miR-506 mimic or GDCDA bile acid suppressed, whereas inhibition of miR-506 by miR-506 inhibitor or lipopolysaccharide (LPS) upregulated the expression of the examined target genes. A different phenotypic presentation of colitis may be related to miR-506 expression. In ascending colons with PSC + UC, upregulation of miR-506 may result in failure of bicarbonate secretion and inhibition of p53, which predisposes to pro-tumorigenic transformation. In contrast, downregulation of miR-506 enhances S1P production, leading to pro-inflammatory signaling.Agnieszka Kempinska-PodhorodeckaMonika AdamowiczEwa OstrycharzMateusz ChmielarzMaciej WójcickiPiotr MilkiewiczMalgorzata MilkiewiczNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Agnieszka Kempinska-Podhorodecka Monika Adamowicz Ewa Ostrycharz Mateusz Chmielarz Maciej Wójcicki Piotr Milkiewicz Malgorzata Milkiewicz Role of miR-506 in ulcerative colitis associated with primary sclerosing cholangitis
description	Abstract Primary sclerosing cholangitis (PSC) is commonly accompanied by ulcerative colitis (UC). MicroRNA-506 modulates expression of genes which are essential for sphingosine-mediated signaling pathway and intestinal mucosa protection. We investigated whether miR-506 and its target genes are involved in phenotypic presentations of colonic inflammation and/or neoplasia. We analyzed serum and colon tissue samples collected from patients with PSC, PSC with concurrent UC (PSC + UC), UC alone, and healthy controls (n = 10 each). MiR-506 was substantially upregulated in ascending colons of PSC and PSC + UC patients, in contrast to sigmoid colons of PSC and UC patients. Upregulation of miR-506 was associated with inhibition of SPHK1, AE2, InsP3R3, and p53. Colonic suppression of miR-506 presented in UC was accompanied by substantially increased DNMT1, SPHK1, and S1P lyase expressions. A functional in vitro analysis in Caco-2 cells showed that the induction of miR-506 activity by miR-506 mimic or GDCDA bile acid suppressed, whereas inhibition of miR-506 by miR-506 inhibitor or lipopolysaccharide (LPS) upregulated the expression of the examined target genes. A different phenotypic presentation of colitis may be related to miR-506 expression. In ascending colons with PSC + UC, upregulation of miR-506 may result in failure of bicarbonate secretion and inhibition of p53, which predisposes to pro-tumorigenic transformation. In contrast, downregulation of miR-506 enhances S1P production, leading to pro-inflammatory signaling.
format	article
author	Agnieszka Kempinska-Podhorodecka Monika Adamowicz Ewa Ostrycharz Mateusz Chmielarz Maciej Wójcicki Piotr Milkiewicz Malgorzata Milkiewicz
author_facet	Agnieszka Kempinska-Podhorodecka Monika Adamowicz Ewa Ostrycharz Mateusz Chmielarz Maciej Wójcicki Piotr Milkiewicz Malgorzata Milkiewicz
author_sort	Agnieszka Kempinska-Podhorodecka
title	Role of miR-506 in ulcerative colitis associated with primary sclerosing cholangitis
title_short	Role of miR-506 in ulcerative colitis associated with primary sclerosing cholangitis
title_full	Role of miR-506 in ulcerative colitis associated with primary sclerosing cholangitis
title_fullStr	Role of miR-506 in ulcerative colitis associated with primary sclerosing cholangitis
title_full_unstemmed	Role of miR-506 in ulcerative colitis associated with primary sclerosing cholangitis
title_sort	role of mir-506 in ulcerative colitis associated with primary sclerosing cholangitis
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/ec2d1e2b90ec47b4a63193e5913e629d
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_version_	1718381235131121664

Role of miR-506 in ulcerative colitis associated with primary sclerosing cholangitis

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