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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| Format: | Article |
| Language: | English |
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Nature Portfolio
2021-05-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-89631-4 |
| _version_ | 1818957019746402304 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-20T11:03:12Z |
| format | Article |
| id | doaj.art-ec2d1e2b90ec47b4a63193e5913e629d |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-20T11:03:12Z |
| publishDate | 2021-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-ec2d1e2b90ec47b4a63193e5913e629d2022-12-21T19:42:57ZengNature PortfolioScientific Reports2045-23222021-05-0111111310.1038/s41598-021-89631-4Role of miR-506 in ulcerative colitis associated with primary sclerosing cholangitisAgnieszka Kempinska-Podhorodecka0Monika Adamowicz1Ewa Ostrycharz2Mateusz Chmielarz3Maciej Wójcicki4Piotr Milkiewicz5Malgorzata Milkiewicz6Department of Medical Biology, Pomeranian Medical UniversityDepartment of Medical Biology, Pomeranian Medical UniversityDepartment of Medical Biology, Pomeranian Medical UniversityDepartment of Medical Biology, Pomeranian Medical UniversityLiver and Internal Medicine Unit, Medical University of WarsawLiver and Internal Medicine Unit, Medical University of WarsawDepartment of Medical Biology, Pomeranian Medical UniversityAbstract 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.https://doi.org/10.1038/s41598-021-89631-4 |
| spellingShingle | 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 Scientific Reports |
| title | 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_short | 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 |
| url | https://doi.org/10.1038/s41598-021-89631-4 |
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