lncRNA MEG3 modulates hepatic stellate cell activation by sponging miR‑145 to regulate PPARγ

Qin,Rong; Huang,Weikang; Huang,Yun; Zhang,Zhibo; Su,Yu; Chen,Sijin; Wang,Hui

doi:10.3892/mmr.2021.12519

lncRNA MEG3 modulates hepatic stellate cell activation by sponging miR‑145 to regulate PPARγ

Authors:
- Rong Qin
- Weikang Huang
- Yun Huang
- Zhibo Zhang
- Yu Su
- Sijin Chen
- Hui Wang
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Affiliations: Department of Gastroenterology, Yan'an Hospital of Kunming, Kunming, Yunnan 650051, P.R. China, Department of Gastroenterology, The Affiliated Yan'an Hospital of Kunming Medical University, Kunming, Yunnan 650051, P.R. China
Published online on: November 2, 2021 https://doi.org/10.3892/mmr.2021.12519
Article Number: 3
Copyright: © Qin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

It is important to determine the mechanism of liver fibrosis for targeted therapy and the development of targeted therapies for liver fibrosis may offer promise for patients with liver disease. Long non‑coding RNAs (lncRNAs) serve a role in hepatic fibrosis. The lncRNA maternally expressed gene 3 (MEG3) has been confirmed to inhibit liver fibrosis. The present study investigated the role of the MEG3 in healthy patients and patients with liver fibrosis. The expression levels of MEG3 and microRNA (miR)‑145 in the serum of healthy volunteers and patients with liver fibrosis and in LX‑2 cells were detected using reverse transcription‑quantitative PCR. A dual‑luciferase reporter assay was used to determine the targeting relationship between MEG3 and miR‑145, and the targeting relationship between miR‑145 and peroxisome proliferator‑activated receptor γ (PPARγ). The protein expression levels of PPARγ, α‑smooth muscle actin (α‑SMA) and collagen I (COL1A1) were detected using western blotting. The expression levels of α‑SMA and COL1A1 were also determined using immunofluorescence. Finally, a Cell Counting Kit‑8 assay was performed to assess the proliferative ability of LX‑2 cells. A significantly reduced MEG3 expression level was demonstrated in serum from patients with liver fibrosis compared with serum from healthy controls. TGF‑β1 induced a significantly decreased MEG3 expression level in LX‑2 human hepatic stellate cells in vitro. The TGF‑β1‑induced increases in cell proliferation and α‑SMA and COL1A1 protein expression levels were reversed following MEG3 overexpression. The results also demonstrated that MEG3 sponged miR‑145 and competed endogenously with miR‑145 to regulate PPARγ. In summary, the present study identified MEG3 as an anti‑fibrotic lncRNA and provided new information regarding the role of MEG3 in liver fibrosis. MEG3 may therefore be a potential target in the treatment of liver fibrosis.

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