LncRNA NEAT1 regulates pulmonary fibrosis through miR-9-5p and TGF-β signaling pathway

Y. Zhang, X.-H. Yao, Y. Wu, G.-K. Cao, D. Han

School of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu, China. xzhmuzhy@xzhmu.edu.cn

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• Respiratory Medicine

OBJECTIVE: Pulmonary fibrosis (PF) is a chronic lung disease with complex pathogenesis and poor prognosis. Studies had demonstrated that long non-coding RNAs (lncRNAs) play an important role in the development of fibrosis. We explored the roles of NEAT1 in PF progression in this study.

PATIENTS AND METHODS: PF tissues and TGF-β1-induced cells were analyzed for the function of NEAT1 in PF progression. qRT-PCR or Western blot was applied to detect NEAT1, miR‑9-5p or protein expressions. PF mice model assay was used to detect the effects of NEAT1 on PF in vivo. Luciferase reporter assay was applied to confirm target relationship between NEAT1 and miR‑9-5p. Correlation of NEAT1 and miR-9-5p was analyzed by Spearman’s method.

RESULTS: We observed that NEAT1 was significantly upregulated while miR-9-5p was downregulated in PF tissues and TGF-β1-induced cells. A negative correlation was exhibited of NEAT1 and miR-9-5p expression in PF tissues. Protein level of p-Smad2 was increased in TGF-β1 induced cells. Furthermore, NEAT1 knockdown increased E-cadherin expression, while decreased N-cadherin, Vimentin, Collagen I, Collagen III and α-smooth muscle actin (α-SMA) expressions in TGF-β1-induced cells. Moreover, NEAT1 could directly target miR-9-5p to regulate the PF induced by TGF-β1. The miR-9-5p overexpression inhibited TGF-β1 and p-Smad2 expression, while NEAT1 overexpression attenuated this effect. In addition, NEAT1 inhibition enhanced E-cadherin expression, and reduced TGF-β1, p-Smad2, N-cadherin, Collagen I, Collagen III, α-SMA and Vimentin expression after BLM treatment.

CONCLUSIONS: Taken together, our findings showed that NEAT1 knockdown attenuated PF via the regulatory of miR-9-5p and TGF-β signaling to repress EMT and might provide new therapeutic targets for PF patients.

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