Exosomal Transfer of LCP1 Promotes Osteosarcoma Cell Tumorigenesis and Metastasis by Activating the JAK2/STAT3 Signaling Pathway.

Abstract

Increasing evidence indicates that lymphocyte cytosolic protein 1 (LCP1) overexpression contributes to tumor progression; however, its role in osteosarcoma (OS) remains unclear. We aimed to investigate the potential effect of LCP1 in OS and the underlying mechanisms. We first demonstrated that LCP1 is upregulated in OS cell lines and tissues. Then, we found that aberrant expression of LCP1 could induce the proliferation and metastasis of OS cells in vitro and in vivo by destabilizing neuregulin receptor degradation protein-1 (Nrdp1) and subsequently activating the JAK2/STAT3 signaling pathway. When coculturing OS cells with bone marrow-derived mesenchymal stem cells (BMSCs) in vitro, we validated that oncogenic LCP1 in OS was transferred from BMSCs via exosomes. Moreover, microRNA (miR)-135a-5p, a tumor suppressor, was found to interact upstream of LCP1 to counteract the pro-tumorigenesis effects of LCP1 in OS. In conclusion, BMSC-derived exosomal LCP1 promotes OS proliferation and metastasis via the JAK2/STAT3 pathway. Targeting the miR-135a-5p/LCP1 axis may have potential in treating OS.

• Authors: Xuhui Ge, Wei Liu, Wene Zhao, Shuang Feng, Ao Duan, Chengyue Ji, Kai Shen, Wanshun Liu, Jiawen Zhou, Dongdong Jiang, Yuluo Rong, Fangyi Gong, Jiaxing Wang, Zhiyang Xu, Xiaoyan Li, Jin Fan, Yongzhong Wei, Jianling Bai, Weihua Cai
• Journal: Molecular therapy. Nucleic acids (Mol Ther Nucleic Acids) Vol. 21 Pg. 900-915 (Sep 04 2020) ISSN: 2162-2531 [Print] United States
• PMID: 32810692 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.