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Research Paper|Volume 13, Issue 1|pp 1212—1235

Therapeutic potential of targeting HSPA5 through dual regulation of two candidate prognostic biomarkers ANXA1 and PSAT1 in osteosarcoma

Xiaojun Tang1,2, Lingli Luo3, Yukun Li4, Hailong Wu5, Qing Hu6, Haiyan Yue7, Xiao He8, Juan Zou4, Shaoxiong Min1,5
  • 1Department of Spinal Surgery, Orthopaedic Medical Center, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, Guangdong Province, China
  • 2Department of Spinal Surgery, The Second Affiliated Hospital, University of South China, Hengyang 421001, Hunan Province, China
  • 3Medical College, Hunan Polytechnic of Environment and Biology, Hengyang 421005, Hunan Province, China
  • 4Hunan Province Key Laboratory of Tumor Cellular and Molecular Pathology, Cancer Research Institute, University of South China, Hengyang 421001, Hunan Province, China
  • 5Department of Spinal Surgery, Peking University Shenzhen Hospital, Shenzhen 518036, Guangdong Province, China
  • 6Department of Pathology, People’s Hospital of Hunan Province, Changsha 410005, Hunan Province, China
  • 7Department of Pathology, The Central Hospital of Shaoyang, Shaoyang 422000, Hunan Province, China
  • 8Department of Breast Surgery, Hunan Provincial Tumor Hospital, Changsha 410005, Hunan Province, China
* Equal contribution
Received: June 19, 2020Accepted: September 3, 2020Published: December 3, 2020
https://doi.org/10.18632/aging.202258

Copyright: © 2020 Tang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Osteosarcoma is the most common primary malignant bone tumor that mostly affects young people’s health. The prognosis of patients with unresectable or recurrent osteosarcoma still remains dismal. Based on gene integration analysis from GEO and TARGET databases by R language, the differentially expressed genes of osteosarcoma patients were identified. Biological molecular function analysis indicated that these genes were importantly enriched in the process of cell adhesion molecule binding. Gene significance highly-related to clinical traits of osteosarcoma was found by weighted gene co-expression network analysis. Additionally, receiver operating characteristic curve analysis was conducted to find prognostic markers in LASSO Cox regression model. Two candidate biomarkers, ANXA1 and PSAT1, for the prognosis of osteosarcoma were detected separately on the basis of WGCNA and LASSO model. Of note, their expression profiles were interrelated with an important therapeutic target HSPA5. In vitro pharmaceutical experiments were performed to explore the biological role and prognostic benefit of candidates. Suppression of HSPA5 effectively upregulated ANXA1 and inhibited PSAT1, resulting in osteosarcoma cell proliferation arrest and apoptosis. These findings suggest that HSPA5 serves as a core molecule for osteosarcoma therapy due to its bidirectional regulation of candidate prognostic biomarkers ANXA1 and PSAT1.