Long noncoding RNA GAS5 inhibits LX-2 cells activation by suppressing NF-κB signalling through regulation of the miR-433-3p/TLR10 axis

长链非编码 RNA GAS5 通过调节 miR-433-3p/TLR10 轴抑制 NF-κB 信号传导,从而抑制 LX-2 细胞活化

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作者:Si-Biao Su, Lin Tao, Xiao-Le Liang, Wen Chen

Aims

Our aims were to reveal the role of GAS5 in the regulation of liver fibrosis.

Background

Liver fibrosis is a common disease that can lead to hepatic failure. Aims: Our aims were to reveal the role of GAS5 in the regulation of liver fibrosis.

Conclusion

LncRNA GAS5 exerts an inhibitory effect on HSC activation by suppressing NF-κB signalling through regulation of the miR-433-3p/TLR10 axis.

Methods

LX-2 human hepatic satellite cells (HSCs) were cultured and activated using TGF-β1 treatment. A CCK-8 assay was performed to assess cell viability. A luciferase assay was employed to monitor the interactions between miR-433-3p and GAS5 or toll-like receptor 10 (TLR10). Western blotting and real-time quantitative PCR (RT-qPCR) were applied to detect the expression levels of α-SMA, Col. I, PCNA-, MMP2-, MMP9-, TLR10-, and NF-κB-related molecules at the protein and RNA levels.

Results

GAS5 and TLR10 were decreased while miR-433-3p was upregulated in TGF-β1-activated LX-2 cells. Upregulation of GAS5 or downregulation of miR-433-3p suppressed HSC activation, and luciferase assays indicated that miR-433-3p binds with GAS5 and the 3'-UTR of TLR10. MiR-433-3p upregulation and TLR10 downregulation rescued the impacts of GAS5 overexpression or miR-433-3p knockdown on LX-2 cells. Upregulation of GAS5 also suppressed the phosphorylation of NF-κB through the miR-433-3p/TLR10 axis.

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