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lncRNA ZFAS1 promotes lung fibroblast-to-myofibroblast transition and ferroptosis via functioning as a ceRNA through miR-150-5p/SLC38A1 axis.
Aging-US ( IF 3.9 ) Pub Date : 2020-05-26 , DOI: 10.18632/aging.103176
Yanni Yang 1 , Wenlin Tai 2 , Nihong Lu 3 , Ting Li 4 , Yongjun Liu 4 , Wenjuan Wu 4 , Zhengkun Li 4 , Lin Pu 4 , Xiaoyuan Zhao 4 , Tao Zhang 4 , Zhaoxing Dong 4
Affiliation  

Pulmonary fibrosis (PF) is a lethal fibrotic lung disease. The role of lncRNAs in multiple diseases has been confirmed, but the role and mechanism of lncRNA zinc finger antisense 1 (ZFAS1) in the progression of PF need to be elucidated further. Here, we found that lncRNA ZFAS1 was upregulated in bleomycin (BLM)-induced PF rats lung tissues and transforming growth factor-β1 (TGF-β1)-treated HFL1 cells, and positively correlated with the expression of solute carrier family 38 member 1 (SLC38A1), which is an important regulator of lipid peroxidation. Moreover, knockdown of lncRNA ZFAS1 significantly alleviated TGF-β1-induced fibroblast activation, inflammation and lipid peroxidation. In vivo experiments showed that inhibition of lncRNA ZFAS1 abolished BLM-induced lipid peroxidation and PF development. Mechanistically, silencing of lncRNA ZFAS1 attenuated ferroptosis and PF progression by lncRNA ZFAS1 acting as a competing endogenous RNA (ceRNA) and sponging miR-150-5p to downregulate SLC38A1 expression. Collectively, our studies demonstrated the role of the lncRNA ZFAS1/miR-150-5p/SLC38A1 axis in the progression of PF, and may provide a new biomarker for the treatment of PF patients.

中文翻译:

lncRNA ZFAS1 通过 miR-150-5p/SLC38A1 轴作为 ceRNA 发挥作用,促进肺成纤维细胞向肌成纤维细胞的转化和铁死亡。

肺纤维化 (PF) 是一种致命的纤维化肺部疾病。lncRNAs在多种疾病中的作用已得到证实,但lncRNA锌指反义1(ZFAS1)在PF进展中的作用和机制有待进一步阐明。在这里,我们发现 lncRNA ZFAS1 在博来霉素 (BLM) 诱导的 PF 大鼠肺组织和转化生长因子-β1 (TGF-β1) 处理的 HFL1 细胞中上调,并与溶质载体家族 38 成员 1 的表达呈正相关。 SLC38A1),是脂质过氧化的重要调节剂。此外,lncRNA ZFAS1 的敲低显着减轻了 TGF-β1 诱导的成纤维细胞活化、炎症和脂质过氧化。体内实验表明,lncRNA ZFAS1 的抑制消除了 BLM 诱导的脂质过氧化和 PF 发展。从机制上讲,lncRNA ZFAS1 的沉默减弱了 lncRNA ZFAS1 作为竞争性内源性 RNA (ceRNA) 和海绵 miR-150-5p 以下调 SLC38A1 表达而导致的铁死亡和 PF 进展。总的来说,我们的研究证明了 lncRNA ZFAS1/miR-150-5p/SLC38A1 轴在 PF 进展中的作用,并可能为 PF 患者的治疗提供新的生物标志物。
更新日期:2020-05-26
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