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长链非编码 RNA-PVT1 通过 miR-497-5p 激活肺成纤维细胞,并受 FOXM1 促进。

LncRNA-PVT1 activates lung fibroblasts via miR-497-5p and is facilitated by FOXM1.

机构信息

Centre for Global Health, Department of Occupational Medicine and Environmental Health, Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China.

Centre for Global Health, Department of Occupational Medicine and Environmental Health, Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China.

出版信息

Ecotoxicol Environ Saf. 2021 Apr 15;213:112030. doi: 10.1016/j.ecoenv.2021.112030. Epub 2021 Feb 16.

Abstract

It is little known about the lncRNA-PVT1 effect on occupational pulmonary fibrosis, although researches show it plays an essential role in cancer. Studies reveal that lung fibroblast activation is one of the key events in silica-induced fibrosis. Here, we found that lncRNA-PVT1 promoted the proliferation, activation, and migration of lung fibroblasts. The isolation of cytoplasmic and nuclear RNA assay and fluorescence in situ hybridization experiment showed that lncRNA-PVT1 was abundantly expressed in the cytoplasm. Luciferase reporter gene assay and RNA pull-down experiment indicated that the cytoplasmic-localized lncRNA-PVT1 could competitively bind miR-497-5p. MiR-497-5p was further observed to attenuate silica-induced pulmonary fibrosis by targeting Smad3 and Bcl2. Moreover, the transcription factor FOXM1 acted as a profibrotic factor by elevating lncRNA-PVT1 transcription in lung fibroblasts. Inhibition of FOXM1 expression with thiostrepton alleviated silica-induced pulmonary fibrosis in vivo. Collectively, we revealed that FOXM1-facilitated lncRNA-PVT1 activates lung fibroblasts via miR-497-5p during silica-induced pulmonary fibrosis, which may provide potential therapeutic targets for pulmonary fibrosis.

摘要

lncRNA-PVT1 对职业性肺纤维化的影响知之甚少,尽管研究表明它在癌症中起着重要作用。研究表明,肺成纤维细胞的激活是二氧化硅诱导纤维化的关键事件之一。在这里,我们发现 lncRNA-PVT1 促进了肺成纤维细胞的增殖、激活和迁移。细胞质和核 RNA 分析和荧光原位杂交实验表明,lncRNA-PVT1 在细胞质中大量表达。荧光素酶报告基因检测和 RNA 下拉实验表明,细胞质定位的 lncRNA-PVT1 可以竞争性结合 miR-497-5p。miR-497-5p 通过靶向 Smad3 和 Bcl2 进一步观察到可减轻二氧化硅诱导的肺纤维化。此外,转录因子 FOXM1 通过提高肺成纤维细胞中的 lncRNA-PVT1 转录来充当促纤维化因子。用硫代丝菌素抑制 FOXM1 的表达可减轻体内二氧化硅诱导的肺纤维化。总之,我们揭示了 FOXM1 促进的 lncRNA-PVT1 通过 miR-497-5p 在二氧化硅诱导的肺纤维化过程中激活肺成纤维细胞,这可能为肺纤维化提供潜在的治疗靶点。

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