Abstract
Background:
This study commenced to uncover the role of long non-coding RNA FBXL19 antisense RNA 1 (FBXL19-AS1) in the development of ulcerative colitis (UC) and its possible mechanism.
Methods:
FBXL19-AS1 expression in the colonic sigmoid mucosa of UC patients was detected. A colitis model was induced in mice using 5% dextran sodium sulfate. Hematoxylin–eosin staining was performed for histopathological examination. Apoptosis was detected by Tunel staining and tissue fibrosis was detected by immunohistochemistry. Also, intestinal permeability was examined. The concentrations of inflammatory factors IL-1β and IL-18 were detected by enzyme-linked immunosorbent assay. The relationship between FBXL19-AS1, miR-339-3p and RHOB was verified by RNA immunoprecipitation assay and dual luciferase reporter assay.
Results:
The expression of FBXL19-AS1 was increased in dextran sodium sulfate (DSS)-induced colitis mouse model. FBXL19-AS1 interference or miR-339-3p overexpression inhibited DSS-induced colonic epithelial cell apoptosis and inflammatory response, and improved intestinal epithelial barrier defects, thereby ameliorating DSS-induced colitis injury in mice. FBXL19-AS1 sponged miR-339-3p while miR-339-3p targeted RHOB. Overexpression of RHOB reversed the protective effect of inhibition of FBXL19-AS1 on DSS-induced colitis in mice.
Conclusion:
FBXL19-AS1 reduces miR-339-3p-mediated targeting of RHOB and aggravates intestinal epithelial barrier defect in DSS-induced colitis in mice.
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This work was financially supported by Cultivation Fund of National Natural Science Foundation (Grant No. qiankehe2018-5764–11).
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he experiment research protocol was approved by the Ethics Committee of Guizhou Provincial People’s Hospital and all experimental procedures conformed with institutional guidelines, and all patients participating in this study provided written informed consent in accordance with the “Helsinki Declaration”, Animal care were approved by Guizhou Provincial People’s Hospital Animal Care Committee and performed according to NIH guidelines (Approval NO. GZ201609BP601).
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13770_2022_479_MOESM1_ESM.tif
Supplementary Fig. 1 Gene expression analysisA. FBXL19-AS1 expression in mouse colon tissue; B. miR-339-3p expression in mouse colon tissue; C. RHOB expression in colon tissue of mice. (TIF 4386 KB)
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Zhao, X., Cui, DJ., Yang, Lc. et al. Long Noncoding RNA FBXL19-AS1-Mediated Ulcerative Colitis-Associated Intestinal Epithelial Barrier Defect. Tissue Eng Regen Med 19, 1077–1088 (2022). https://doi.org/10.1007/s13770-022-00479-9
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DOI: https://doi.org/10.1007/s13770-022-00479-9