Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

LncRNA MALAT1: A potential therapeutic target in DSS-induced ulcerative colitis progression in vitro

Baoqin Zhang, Tiantian Li, Chao Wang, Jing Han, Baiqing Wang, Guangbin Sun

Department of Gastroenterology, Tianjin Fifth Central Hospital, Tianjin 300450, China;

For correspondence:- Guangbin Sun Email: cvb7853@126.com Tel:+8618273509271

Accepted: 26 March 2020 Published: 30 September 2020

Citation: Zhang B, Li T, Wang C, Han J, Wang B, Sun G. LncRNA MALAT1: A potential therapeutic target in DSS-induced ulcerative colitis progression in vitro. Trop J Pharm Res 2020; 19(9):1871-1877 doi: 10.4314/tjpr.v19i9.11

© 2020 The authors.
This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited..

Abstract

Purpose: Ulcerative colitis is a severe disease affecting human health worldwide. Studies have shown that lncRNA MALAT1 has a significant correlation with breast, pancreatic, colon and liver cancers, but its effects on colitis is yet to be discovered. In this study, the potential role of lncRNA MALAT1 and the underlying molecular mechanism in DSS-induced colitis were investigated in vitro.

Methods: Colorectal mucosal cell line FHC was induced with dextran sulphate sodium (DSS) to form an in vitro colitis model. Transfection procedure was employed to up- or down-regulate the expressions of lncRNA MALAT1 or miR-30c-5p in FHC cells. Cell viabilities were detected by CCK-8 assay. RT-qPCR was applied for evaluating gene expressions in normal FHC and DSS-induced FHC cell lines, while protein expression levels of target genes were examined by Western blot analysis. Starbase was used to predict the molecular interaction between MALAT1 and miR-30c-5p, while luciferase reporter assay was utilized to verify the binding sites between the two genes.

Results: expression of MALAT1 in the DSS-induced FHC cells was high with low cell viabilities, compared to the normal FHC cells. In the DSS-induced colitis-like FHC cells, overexpression of MALAT1 inhibited cell viabilities, while its downregulation promoted it. MiR-30c-5p directly targets MALAT1 and inhibited its expression in DSS-treated FHC cells. Upregulation of miR-30c-5p increased cell viabilities. Bcl-xL expression was inhibited by the up-regulation of MALAT1, while that of Bax was enhanced and the mimics of miR-30c-5p reversed these observations, suggesting that the enhancement of apoptosis promoted by oe-MALAT1 could be inhibited by miR-30c-5p. The interaction between MALAT1 and miR-30c-5p regulated NF-κB/TGF-β/Wnt-β-catenin signaling pathway.

Conclusion: Overexpression of MALAT1 led to inhibition of cell viability, while apoptosis and inflammation were promoted by targeting miR-30c-5p via NF-κB/TGF-β/Wnt-β-catenin signaling pathway. These findings suggest MALAT1 as a therapeutic target for treating colitis.

Keywords: Colitis, MALAT1, miR-30c-5p, NF-κB/TGF-β/Wnt-β-catenin