Preprint Article Version 1 This version is not peer-reviewed

Oncomir  Microrna-346  is Upregulated  in Ascending but Not Sigmoid Colon in Patients with Primary Sclerosing Cholangitis with Concurrent Ulcerative Colitis.

Version 1 : Received: 13 July 2018 / Approved: 13 July 2018 / Online: 13 July 2018 (17:36:38 CEST)

How to cite: Kempinska-Podhorodecka, A.; Blatkiewicz, M.; Wunsch, E.; Krupa, L.; Gutkowski, K.; Milkiewicz, P.; Milkiewicz, M. Oncomir  Microrna-346  is Upregulated  in Ascending but Not Sigmoid Colon in Patients with Primary Sclerosing Cholangitis with Concurrent Ulcerative Colitis.. Preprints 2018, 2018070247 (doi: 10.20944/preprints201807.0247.v1). Kempinska-Podhorodecka, A.; Blatkiewicz, M.; Wunsch, E.; Krupa, L.; Gutkowski, K.; Milkiewicz, P.; Milkiewicz, M. Oncomir  Microrna-346  is Upregulated  in Ascending but Not Sigmoid Colon in Patients with Primary Sclerosing Cholangitis with Concurrent Ulcerative Colitis.. Preprints 2018, 2018070247 (doi: 10.20944/preprints201807.0247.v1).

Abstract

Primary sclerosing cholangitis (PSC) is a cholestatic liver disorder frequently associated with ulcerative colitis (UC). Patients with PSC and UC have higher risk of colorectal neoplasia than patients with UC without PSC. Oncogenic properties of micro RNA 346 (miR-346) have been recently reported. In this study we investigated expressions of miR-346 and its two target genes i.e. the receptor of vitamin D (VDR) and the tumor necrosis factor α (TNF-α), which are known to modulate carcinogenesis. Biopsies from ascending and sigmoid colon were obtained from patients with PSC with and without UC, patients with UC and healthy controls. MiR-346 expression was increased in ascending but not sigmoid colon of patients with PSC and UC when compared to other analyzed groups (p<0.001 for all). In patients with UC an exceptionally low colonic expression of miRNA-346 was accompanied by the increase in VDR expression, and the extensive upregulation of TNF-α gene which protein product is known to be cytotoxic to tumor cells at high concentration. In summary, a substantial upregulation of miRNA-346 in ascending colon of patients with PSC and UC may be responsible for the inhibition of VDR and TNF-α signaling -pathway which may result in an inadequate suppression of neoplasia.

Subject Areas

vitamin D receptor, cytokines, miR-346, primary sclerosing cholangitis, colorectal cancer

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