Abstract
The role of long non-coding RNA (lncRNA) in idiopathic pulmonary fibrosis (IPF) is poorly understood. We found a novel lncRNA-ITPF that was upregulated in IPF. Bioinformatics and in vitro translation verified that lncITPF is an actual lncRNA, and its conservation is in evolution. Northern blot and rapid amplification of complementary DNA ends were used to analyze the full-length sequence of lncITPF. RNA fluorescence in situ hybridization and nucleocytoplasmic separation demonstrated that lncITPF was mainly located in the nucleus. RNA sequencing, chromatin immunoprecipitation (ChIP)-qPCR, CRISPR-Cas9 technology, and promoter activity analysis showed that the fibrotic function of lncITPF depends on its host gene integrin β-like 1 (ITGBL1), but they did not share the same promoter and were not co-transcribed. Luciferase activity, pathway inhibitors, and ChIP-qPCR showed that smad2/3 binds to the lncITPF promoter, and TGF-β1-smad2/3 was the upstream inducer of the fibrotic pathway. Furthermore, RNA-protein pull-down, liquid chromatography-mass spectrometry (LC-MS), and protein-RNA immunoprecipitation showed that lncITPF regulated H3 and H4 histone acetylation in the ITGBL1 promoter by targeting heterogeneous nuclear ribonucleoprotein L. Finally, sh-lncITPF was used to evaluate the therapeutic effect of lncITPF. Clinical analysis showed that lncITPF is associated with the clinicopathological features of IPF patients. Our findings provide a therapeutic target or diagnostic biomarker for IPF.