2. Academic Validation
  3. USP3 promotes osteosarcoma progression via deubiquitinating EPHA2 and activating the PI3K/AKT signaling pathway

USP3 promotes osteosarcoma progression via deubiquitinating EPHA2 and activating the PI3K/AKT signaling pathway

  • Cell Death Dis. 2024 Mar 26;15(3):235. doi: 10.1038/s41419-024-06624-7.
Anan Li # 1 2 3,  Shijiang Wang # 1 2 3,  Jiangbo Nie 1 2 3,  Shining Xiao 1 2 3,  Xinsheng Xie 2 3,  Yu Zhang 1 2 3,  Weilai Tong 1 2 3,  Geliang Yao 1 2 3,  Ning Liu 1 2 3,  Fan Dan 1 2 3,  Zhiguo Shu 1 2 3,  Jiaming Liu 1 2 3,  Zhili Liu 4 5 6,  Feng Yang 7 8 9 10
Affiliations

Affiliations

  • 1 Orthopedic Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China.
  • 2 Medical Innovation Center, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China.
  • 3 Institute of Spine and Spinal Cord, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China.
  • 4 Orthopedic Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China. zhili-liu@ncu.edu.cn.
  • 5 Medical Innovation Center, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China. zhili-liu@ncu.edu.cn.
  • 6 Institute of Spine and Spinal Cord, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China. zhili-liu@ncu.edu.cn.
  • 7 Orthopedic Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China. feng_yang@ncu.edu.cn.
  • 8 Medical Innovation Center, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China. feng_yang@ncu.edu.cn.
  • 9 Institute of Spine and Spinal Cord, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China. feng_yang@ncu.edu.cn.
  • 10 Postdoctoral Innovation Practice Base, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China. feng_yang@ncu.edu.cn.
  • # Contributed equally.
PMID: 38531846 DOI: 10.1038/s41419-024-06624-7
Abstract

Ubiquitin-Specific Protease 3 (USP3) plays an important role in the progression of various tumors. However, the role of USP3 in osteosarcoma (OS) remains poorly understood. The aim of this study was to explore the biological function of USP3 in OS and the underlying molecular mechanism. We found that OS had higher USP3 expression compared with that of normal bone tissue, and high expression of USP3 was associated with poor prognosis in patients with OS. Overexpression of USP3 significantly increased OS cell proliferation, migration, and invasion. Mechanistically, USP3 led to the activation of the PI3K/Akt signaling pathway in OS by binding to EphA2 and then reducing its protein degradation. Notably, the truncation mutant USP3-F2 (159-520) interacted with EphA2, and amino acid 203 was found to play an important role in this process. And knockdown of EphA2 expression reversed the pro-tumour effects of USP3-upregulating. Thus, our study indicates the USP3/EphA2 axis may be a novel potential target for OS treatment.

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