Suppression of miR-330-3p alleviates DSS-induced ulcerative colitis and apoptosis by upregulating the endoplasmic reticulum stress components XBP1.

Background: This study aimed to explore the biological activities of miR-330-3p in dextan sulphate sodium (DSS)-induced ulcerative colitis and apoptosis and the direct target of miR-330-3p in this process. HT-29 cells and male C57BL/6 mice were used to examine the function of miR-330-3p in vitro and in vivo, respectively. Expression of miRNA and mRNA was measured using quantitative real time PCR (qRT-PCR). Western blotting was used to measure the change of protein expression. Flow cytometry was used to determine cell apoptosis and luciferase assay was used to confirm the direct target of miR-330-3p.
Results: miR-330-3p expression was increased by DSS in both HT-29 cells and mice. Upregulation miR-330-3p induced cell apoptosis, mice weight loss and ulcerative colitis in vivo, which could prevent by suppression of miR-330-3p. Cell apoptosis related protein expression, cleaved caspase-3 and cleaved PARP was also inhibited by miR-330-3p overexpression and elevated by miR-330-3p inhibition both in vitro and in vivo. Luciferase assay confirmed that 3' untranslated region (3'-UTR) of XBP1 is the directed target of miR-330-3p and Western blotting results have showed that protein expression of XBP1 was decreased by miR-330-3p mimics and increased by miR-330-3p inhibitor.
Conclusion: miR-330-3p is upregulated by DSS in both HT-29 cells and mice and promoted ulcerative colitis and cell apoptosis by targeting of 3'-UTR of XBP1, which is a key component of ER stress. Inhibition of miR-330-3p prevent DSS-induced ulcerative colitis and cell apoptosis mediated by upregulation of XBP1 expression.