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

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

Molecular Therapy: Nucleic Acids (Sep 2020)

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

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

Affiliations

Xuhui Ge: Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China
Wei Liu: Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China
Wene Zhao: Department of Analytical & Testing Center, Nanjing Medical University, Nanjing, Jiangsu 211166, China
Shuang Feng: Department of Encephalopathy, The Third Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210001, China
Ao Duan: Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China
Chengyue Ji: Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China
Kai Shen: Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China
Wanshun Liu: Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China
Jiawen Zhou: Research Center for Bone and Stem Cells, Department of Human Anatomy, Key Laboratory for Aging & Disease, The State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu 211166, China
Dongdong Jiang: Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China
Yuluo Rong: Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China
Fangyi Gong: Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China
Jiaxing Wang: Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China
Zhiyang Xu: Department of Analytical & Testing Center, Nanjing Medical University, Nanjing, Jiangsu 211166, China
Xiaoyan Li: Department of Analytical & Testing Center, Nanjing Medical University, Nanjing, Jiangsu 211166, China
Jin Fan: Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China
Yongzhong Wei: Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China; Corresponding author: Yongzhong Wei, Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China.
Jianling Bai: Department of Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu 211166, China; Corresponding author: Jianling Bai, Department of Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu 211166, China.
Weihua Cai: Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China; Corresponding author: Weihua Cai, Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China.

Journal volume & issue: Vol. 21
pp. 900 – 915

Abstract

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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.

Published in Molecular Therapy: Nucleic Acids

ISSN: 2162-2531 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: https://www.cell.com/molecular-therapy-family/nucleic-acids/latest-content

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