Long non‑coding RNA MBI‑52 inhibits the development of liver fibrosis by regulating the microRNA‑466g/SMAD4 signaling pathway

Li,Yazhou; Liu,Peixiao; Wei,Feipeng

doi:10.3892/mmr.2021.12549

Long non‑coding RNA MBI‑52 inhibits the development of liver fibrosis by regulating the microRNA‑466g/SMAD4 signaling pathway

Authors:
- Yazhou Li
- Peixiao Liu
- Feipeng Wei
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Affiliations: Department of Pain Intervention, Baoji High‑tech People's Hospital, Baoji, Shaanxi 721000, P.R. China, Department of Cardiopulmonary Rehabilitation, Xi'an International Medical Center Hospital, Xi'an, Shaanxi 710000, P.R. China, Department of Interventional Radiology, Tangdu Hospital, Air Force Military Medical University, Xi'an, Shaanxi 710038, P.R. China
Published online on: December 1, 2021 https://doi.org/10.3892/mmr.2021.12549
Article Number: 33
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Liver fibrosis is a wound healing response triggered by liver injury. In severe cases, it may develop into liver cirrhosis, liver cancer and liver failure. Long non‑coding RNAs (lncRNAs) play key roles in the development of liver fibrosis. The present study aimed to investigate the role of lncRNA‑MBI‑52 (lnc‑MBI‑52) in the progression of liver fibrosis. Carbon tetrachloride (CCl₄)‑induced injury was performed to establish a mouse liver fibrosis model, and exogenous transforming growth factor‑β1 was used to establish a hepatic stellate cell (HSC) activation model. Reverse transcription‑quantitative PCR and western blot analyses were performed to detect mRNA and protein expression, respectively. RNA pull‑down assay was performed to assess the interaction between microRNA (miR)‑466g and lnc‑MBI‑52 or SMAD4. Dual‑luciferase reporter assay was performed to verify the target of miR‑466g. lnc‑MBI‑52 was overexpressed in CCl₄‑induced mouse liver fibrosis models and activated HSCs. lnc‑MBI‑52 knockdown suppressed liver fibrosis in vitro. Moreover, knockdown of lnc‑MBI‑52 downregulated α‑smooth muscle actin and collagen type I expression. In addition, lnc‑MBI‑52 and SMAD4 were identified as targets of miR‑466g. The effects of lnc‑MBI‑52 on HSC activation were reversed following transfection with miR‑466g mimics or SMAD4 knockdown. lnc‑MBI‑52 miR‑466g significantly decreased lnc‑MBI‑52 expression, while overexpression of lnc‑MBI‑52 suppressed miR‑466g expression. The results of the RNA pull‑down assay confirmed the interaction between miR‑466g and lnc‑MBI‑52. Taken together, lnc‑MBI‑52 induced liver fibrosis by regulating the miR‑466g/SMAD4 axis, which may provide a new possible strategy for liver fibrosis.

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