LncRNA Hoxaas3 promotes lung fibroblast activation and fibrosis by targeting miR-450b-5p to regulate Runx1

Author:

Lin ShuangORCID,Zhang Rui,Xu Lei,Ma Rui,Xu Liming,Zhu Linghua,Hu Jian,An Xiaoxia

Abstract

AbstractLong noncoding RNAs (lncRNAs) participate in organ fibrosis and various pulmonary diseases, but its role in idiopathic pulmonary fibrosis (IPF) is not fully understood. In this study, we found lncRNA Hoxaas3 (Hoxaas3) was up-regulated in the mice model of BLM-induced PF and TGF-β1-induced fibrogenesis in lung fibroblasts (LF). Overexpression of Hoxaas3 promoted fibrogenesis, whereas Hoxaas3 inhibition attenuated lung fibrosis both in vitro and in vivo, through regulation of miR-450b-5p. Furthermore, miR-450b-5p inhibition stimulated fibrogenesis by regulating runt-related transcription factor 1 (Runx1), whereas up-regulation of miR-450b-5p alleviated fibrogenesis in LF. Mechanistically, our study showed that Hoxaas3 regulated lung fibroblast activation and fibrogenesis by acting as a competing endogenous RNA for miR-450b-5p: Hoxaas3 decreased the expression of miR-450b-5p to stimulate level and activity of Runx1 and induced fibrotic LF, whereas Runx1 inhibition alleviated the pro-fibrotic effect of Hoxaas3. In addition, Hoxaas3 was regulated by TGF-β1/Smad4 pathway as its transcriptional target. In conclusion, our study showed the role and mechanism of the TGF-β1/Smad4- Hoxaas3–miR-450b-5p–Runx1 axis for a better understanding of PF, demonstrated Hoxaas3 maybe a new diagnostic biomarker or potential therapeutic target for IPF.

Publisher

Springer Science and Business Media LLC

Subject

Cancer Research,Cell Biology,Cellular and Molecular Neuroscience,Immunology

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3