MALAT1 promotes liver fibrosis by sponging miR‑181a and activating TLR4‑NF‑κB signaling

Wang,Yinghui; Mou,Qiuju; Zhu,Zixin; Zhao,Luqiang; Zhu,Lili

doi:10.3892/ijmm.2021.5048

MALAT1 promotes liver fibrosis by sponging miR‑181a and activating TLR4‑NF‑κB signaling

Authors:
- Yinghui Wang
- Qiuju Mou
- Zixin Zhu
- Luqiang Zhao
- Lili Zhu
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Affiliations: School of Clinical Laboratory Science, Guizhou Medical University, Guiyang, Guizhou 550004, P.R. China, Department of Blood Transfusion, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou 550004, P.R. China, Department of Basic Medical College, Guizhou Medical University, Guiyang, Guizhou 550025, P.R. China
Published online on: October 13, 2021 https://doi.org/10.3892/ijmm.2021.5048
Article Number: 215
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The aim of the present study was to investigate whether long non‑coding RNA metastasis associated lung adenocarcinoma transcript 1 (MALAT1) could modulate activation and inflammation of hepatic stellate cell (HSCs) via regulation of a microRNA (miR)‑181a‑toll like receptor (TLR)4/nuclear factor (NF)‑κB axis, thereby contributing to the development of liver fibrosis. A total of 151 patients with liver fibrosis were recruited, and the serum levels of alanine transaminase, aspartate aminotransferase and albumin were determined. Transforming growth factor (TGF)‑β1 and LPS were used to activate and induce inflammation in the human HSC cell line LX2. MALAT1 was knocked using small interfering RNA or overexpressed, and an inhibitor and mimic of miR‑181a‑5p were used to examine the effect of MALAT1 and miR‑181a‑5p on the activation and inflammation of LX2 cells. Both MALAT1 and miR‑181a‑5p expression performed well in their ability to differentiate patients with liver fibrosis from healthy volunteers, and MALAT1 expression was associated with the severity of liver fibrosis. The expression levels of TLR4 and NF‑κB were increased after stimulation with LPS or TGF‑β1, but MALAT1 knockdown or miR‑181a‑5p mimic transfection abrogated this increase. Moreover, the TGF‑β1‑induced increase in viability, proliferation, migration, adhesion and collagen production, and the LPS‑induced inflammation of LX2 cells were all reversed after MALAT1 knockdown or transfection with miR‑181a‑5p mimic. The MALAT1/miR‑181a‑5p axis was involved in regulating collagen production and inflammation by activating TLR4/NF‑κB signaling, which may be conducive to liver fibrosis treatment in the future.

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