Effect of Long Noncoding RNA H19 Overexpression on Intestinal Barrier Function and Its Potential Role in the Pathogenesis of Ulcerative Colitis

• Published in: Inflammatory bowel diseases 2016-11, Vol.22 (11), p.2582-2592
• Main Authors: Chen, Shan-Wen, Wang, Peng-Yuan, Liu, Yu-Cun, Sun, Lie, Zhu, Jing, Zuo, Shuai, Ma, Ju, Li, Teng-Yu, Zhang, Jun-Ling, Chen, Guo-Wei, Wang, Xin, Zhu, Qiu-Ru, Zheng, You-Wen, Chen, Ze-Yang, Yao, Zi-Hao, Pan, Yi-Sheng
• Format: Article
• Language: English
• Subjects: Colitis, Ulcerative - genetics; Colitis, Ulcerative - physiopathology; Humans; Intestinal Mucosa - physiology; Real-Time Polymerase Chain Reaction; Receptors, Calcitriol - metabolism; RNA, Long Noncoding - metabolism; RNA, Messenger - metabolism; Signal Transduction - genetics
• ISSN: 1078-0998; 1536-4844
• DOI: 10.1097/MIB.0000000000000932

Recently, long noncoding RNA (lncRNA) H19 has been reported to be related with VDR signaling and the development of inflammatory diseases including osteoarthritis. The aim of this study was to investigate the correlation between the expression level of H19 and VDR in ulcerative colitis (UC) tissues and to investigate the effect of H19 overexpression on intestinal epithelial barrier function. The expression level of H19, miR-675-5p, and VDR in UC tissues and paired normal tissues collected from 12 patients with UC was investigated by quantitative real-time polymerase chain reaction. Caco-2 monolayers were used to test the effect of H19 and miR-675-5p overexpression on the intestinal epithelial barrier function and the status of tight junction proteins and VDR. Luciferase assay was used to validate the target site of miR-675-5p in the 3'UTR of VDR mRNA. The expression of H19 was found to be negatively correlated with the expression of VDR in UC tissues (r = 0.5369, P < 0.05). The expression of miR-675-5p was also found to be negatively correlated with the expression of VDR in UC tissues (r = 0.5233, P < 0.01). H19 overexpression increased Caco-2 monolayer permeability and decreased the expression of tight junction proteins and VDR, which was significantly attenuated by cotransfection with miR-675-5p inhibitors. The 3'UTR of VDR mRNA was validated to be one of the direct targets of miR-675-5p. This study reveals the destructive effect of H19 overexpression on intestinal epithelial barrier function and suggests a potential role of H19 in the development of UC. In addition, H19 overexpression may be one of the mechanisms underlying the decreased expression of VDR in UC tissues and the interaction between H19 and VDR signaling may provide potential therapeutic targets for UC.