CircHECTD1 mediates pulmonary fibroblast activation <i>via</i> HECTD1

Published on 2019-11-28T13:06:29Z (GMT) by
<div>Background:<p>Circular RNA (circRNA), a new class of noncoding RNA, has been shown to be important in silicosis due to its unique role as a transcription regulator or as a sponge of small RNA regulators. Here, the mechanisms underlying circHECTD1/HECTD1 in fibroblast activation and subsequent fibrosis induced by SiO<sub>2</sub> were investigated.</p>Methods:<p>Primary human pulmonary fibroblasts (HPF-a) were utilized, combined with quantitative real-time PCR (qRT-PCR) and fluorescence in situ hybridization (FISH) assays. LC3B-LV-RFP lentivirus was used to evaluate the role of autophagy. The CRISPR/Cas9 system was applied to specifically knock down HECTD1, combined with MTT, BrdU, and migration assays, to explore the functional changes induced by SiO<sub>2</sub>.</p>Results:<p>After exposure to SiO<sub>2</sub>, the circHECTD1 level was decreased, which was associated with an increase in HECTD1 in HPF-a cells. SiO<sub>2</sub>-induced autophagy was reversed by either circHECTD1 overexpression or HECTD1 knockdown in HPF-a cells, with restored SiO<sub>2</sub>-induced fibroblast activation, proliferation, and migration <i>via</i> downstream autophagy. The lungs of mice exposed to SiO<sub>2</sub> confirmed the upregulation of HECTD1 in pulmonary fibroblasts.</p>Conclusions:<p>Our data suggested a link between circHECTD1/HECTD1 and fibroblast activation with subsequent fibrosis induced by SiO<sub>2</sub>, providing novel insight into the potential of circHECTD1/HECTD1 to be a therapeutic target for silicosis.</p></div>

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Chu, Han; Wang, Wei; Luo, Wei; Zhang, Wei; Cheng, Yusi; Huang, Jie; et al. (2019): CircHECTD1 mediates pulmonary fibroblast activation via HECTD1. SAGE Journals. Collection.