Exosomal lncRNA HOTAIR promotes osteoclast differentiation by targeting TGF-β/PTHrP/RANKL pathway.

Abstract

Bone tissue is a common metastatic site of lung cancer, and bone metastasis is characterized by abnormal differentiation and malfunction of osteoclast, and the roles of exosomes derived from lung cancer have attracted much attention. In our study, we found that the level of HOTAIR expression in A549 and H1299 exosomes was higher than those of normal lung fibrocytes. Overexpression of HOTAIR in A549 and H1299 exosomes promoted osteoclast differentiation. Furthermore, A549-Exos and H1299-Exos targeted bone tissues, and bone formation was significantly inhibited in vivo. Mechanistically, exosomal lncRNA HOTAIR promoted bone resorption by targeting TGF-β/PTHrP/RANKL pathway.

• Authors: Chengcheng Zhang, Jiyong Yang, Zhiyao Zhu, Jingru Qin, Lu Yang, Xiaoxue Zhao, Wan Su, Yuejiao Cai, Jia Yang, Fengying Wang, Wenlian Chen, Honggang Gu, Haibin Deng, Zhongqi Wang
• Journal: Basic & clinical pharmacology & toxicology (Basic Clin Pharmacol Toxicol) Vol. 132 Issue 3 Pg. 242-252 (Mar 2023) ISSN: 1742-7843 [Electronic] England
• PMID: 36482064 (Publication Type: Journal Article)
• Copyright: © 2022 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society). Published by John Wiley & Sons Ltd.

Chemical References

• HOTAIR long untranslated RNA, human
• Parathyroid Hormone-Related Protein
• RANK Ligand
• RNA, Long Noncoding
• Transforming Growth Factor beta

Topics

• Humans
• Cell Differentiation (genetics)
• Exosomes (genetics)
• Lung Neoplasms (genetics, metabolism, pathology)
• Osteoclasts (metabolism)
• Parathyroid Hormone-Related Protein (metabolism)
• RANK Ligand (metabolism)
• RNA, Long Noncoding (genetics, metabolism)
• Transforming Growth Factor beta (metabolism)