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bioRxiv · 10.1101/2021.02.05.430002

Suppression of miR-199a-5p alleviates ulcerative colitis by upregulating endoplasmic reticulum stress component XBP1

Wang, S.·Shen, L.·Peng, S.·Tian, M.·Li, X.·Luo, H.
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Abstract

Aims: This study aimed to explore the biological activities of miR-199a-5p in dextran sulphate sodium (DSS)-induced ulcerative colitis and apoptosis and identify the direct target of miR-199a-5p in this process. Main methods: HT-29 cells and C57BL/6 mice were used to examine the function of miR-199a-5p in vitro and in vivo, respectively. Expression of miRNA and mRNA was measured using quantitative real-time PCR and western blotting was used to measure the change in protein expression. Flow cytometry was subsequently employed to determine cell apoptosis, and a luciferase assay was used to confirm the direct target of miR-199a-5p. Results: Expression of miR-199a-5p was increased by DSS treatment in mice. In parallel, miR-199a-5p is found to be involved in endoplasmic reticulum stress (ERS) and cell apoptosis in HT-29 cells, and its upregulation induced ERS, apoptosis, weight loss, and ulcerative colitis in mice in vivo, which could be prevented by the suppression of miR-199a-5p. Luciferase assay confirmed that the 3' untranslated region (3'-UTR) of XBP1 is the target binding site of miR-199a-5p. Conclusion: miR-199a-5p promotes ulcerative colitis and cell apoptosis by targeting the 3'-UTR of XBP1. Our findings reveal a new regulatory mechanism for ERS signaling and suggest that miR-199a-5p might be a potential target for UC therapy.

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Wang, S., Shen, L., Peng, S., Tian, M., Li, X., Luo, H.. 2021-02-06. Suppression of miR-199a-5p alleviates ulcerative colitis by upregulating endoplasmic reticulum stress component XBP1. https://doi.org/10.1101/2021.02.05.430002

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