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.

尽管研究表明lncRNA-PVT1对职业性肺纤维化的作用尚不清楚，但目前尚不清楚。研究表明，肺成纤维细胞活化是二氧化硅诱导的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，活化和迁移。细胞质和核RNA分析的分离以及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，胞质定位的lncRNA-PVT1可以竞争性结合miR-497-5p。进一步观察到，MiR-497-5p通过靶向Smad3和Bcl2来减轻二氧化硅诱导的肺纤维化。而且，转录因子FOXM1通过升高肺成纤维细胞中的lncRNA-PVT1转录而充当纤维化因子。硫代链霉菌素抑制FOXM1表达可减轻二氧化硅诱导的体内肺纤维化。总的来说，我们揭示了在二氧化硅诱导的肺纤维化过程中，FOXM1促进的lncRNA-PVT1通过miR-497-5p激活了肺成纤维细胞，这可能为肺纤维化提供潜在的治疗靶点。