Akademik Veri Yönetim Sistemi
JOURNAL OF CELLULAR BIOCHEMISTRY, cilt.122, sa.8, ss.882-896, 2021 (SCI-Expanded)
Long noncoding RNAs (LncRNAs) regulate epithelial-mesenchymal transition (EMT). EMT involves myofibroblast differentiation and pulmonary fibrosis (PF). We aimed to determine the expression profiles of HOTAIR, CARLo-5, and CD99P1 LncRNAs in EMT-mediated myofibroblast differentiation in A549 cells and fibrotic human lungs and to explain their roles. A group of A549s was stimulated with transforming growth factor beta (TGF-beta; 5 ng/ml) to induce EMT. The remaining A549s were incubated with 20 mu M FH535 after 24 h of TGF-beta treatment to inhibit EMT. A549s were collected at 0, 24, 36, and 48 h. Expressions of three LncRNAs and protein/genes related to EMT, myofibroblast differentiation, and PF were assayed by quantitative reverse-transcription polymerase chain reaction and Western blot analysis in A549s and fibrotic human lungs. The targets of three LncRNAs were investigated by bioinformatics methods. TGF-beta stimulation resulted in increased expressions of three LncRNAs, ACTA2, COL1A1, SNAI1, CTNNB1, TCF4, LEF1, alpha-SMA, and active-beta-catenin, and decreased E-cadherin at 24, 36, and 48 h in A549s. FH535 treatment regressed these alterations. But it increased HOTAIR expression at 36 h and did not increase E-cadherin at 48 h. Fibrotic human lungs were characterized by increased expressions of HOTAIR, CARLo-5, CD99P1, and miR-214, decreased expressions of miR-148b, miR-218-1, miR-7-1, and the presence of CARLo-5 and CD99P1 in HDAC1-LncRNAs coprecipitation products, but not HOTAIR. Bioinformatic analysis showed the interactions of three LncRNAs with both proteins and at least 13 microRNAs related to EMT and PF. In conclusion, HOTAIR, CARLo-5, and CD99P1 can regulate EMT-mediated myofibroblast differentiation through interacting with proteins and miRNAs associated with EMT and PF. These LncRNAs can be considered as potential targets to decrease EMT for treating PF.