LncRNA SATB2-AS1 promotes tumor growth and metastasis and affects the tumor immune microenvironment in osteosarcoma by regulating SATB2

Peipei Wang; Jianwei Zhu; Qingqin Long; Yan Wang; Huihua Xu; Huimin Tao; Biwen Wu; Jiajun Li; Yong Wu; Sihong Liu

Journal of Bone Oncology (Aug 2023)

LncRNA SATB2-AS1 promotes tumor growth and metastasis and affects the tumor immune microenvironment in osteosarcoma by regulating SATB2

Peipei Wang,
Jianwei Zhu,
Qingqin Long,
Yan Wang,
Huihua Xu,
Huimin Tao,
Biwen Wu,
Jiajun Li,
Yong Wu,
Sihong Liu

Affiliations

Peipei Wang: Department of Oncology, the Second Affiliated Hospital, and School of Biomedical Sciences and Engineering, Guangzhou International Campus, South China University of Technology, Guangzhou, Guangdong 510180, PR China; Department of Oncology, the Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong 510180, PR China; Guangzhou First People’s Hospital, Guangzhou, Guangdong 510180, PR China
Jianwei Zhu: Department of Orthopaedics, the Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong 510180, PR China; Guangzhou First People’s Hospital, Guangzhou, Guangdong 510180, PR China
Qingqin Long: Department of Oncology, the Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong 510180, PR China; Guangzhou First People’s Hospital, Guangzhou, Guangdong 510180, PR China
Yan Wang: Department of Orthopaedics, the Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong 510180, PR China; Guangzhou First People’s Hospital, Guangzhou, Guangdong 510180, PR China
Huihua Xu: Department of Orthopaedics, the Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong 510180, PR China; Guangzhou First People’s Hospital, Guangzhou, Guangdong 510180, PR China
Huimin Tao: Department of Oncology, the Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong 510180, PR China; Guangzhou First People’s Hospital, Guangzhou, Guangdong 510180, PR China
Biwen Wu: Department of Oncology, the Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong 510180, PR China; Guangzhou First People’s Hospital, Guangzhou, Guangdong 510180, PR China
Jiajun Li: Department of Oncology, the Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong 510180, PR China; Guangzhou First People’s Hospital, Guangzhou, Guangdong 510180, PR China
Yong Wu: Department of Oncology, the Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong 510180, PR China; Guangzhou First People’s Hospital, Guangzhou, Guangdong 510180, PR China; Corresponding authors at: Guangzhou First People’s Hospital, Guangzhou, Guangdong 510180, PR China.
Sihong Liu: Department of Orthopaedics, the Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong 510180, PR China; Guangzhou First People’s Hospital, Guangzhou, Guangdong 510180, PR China; Corresponding authors at: Guangzhou First People’s Hospital, Guangzhou, Guangdong 510180, PR China.

Journal volume & issue: Vol. 41
p. 100491

Abstract

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Our previous report has identified a lncRNA SATB2-AS1, which was significantly up-regulated in osteosarcoma tissue and promotes the proliferation of osteosarcoma cells in vitro. However, the mechanisms of SATB2-AS1 regulating the growth and metastasis of osteosarcoma cells in vivo and its role in the prognosis of osteosarcoma patients are still unclear. In this study, the transcriptome sequencing data of 87 patients with osteosarcoma from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database and 7 patients from our clinical center (GZFPH) was used to evaluate the importance of SATB2-AS1 and SATB2 on the prognosis. The effect of SATB2-AS1 on the growth and metastasis of osteosarcoma cells in vivo was verified by a mouse tumor model. The potential mechanisms of SATB2-AS1 regulating SATB2 were further explored by dual-luciferase reporter gene assay, RNA pull-down assay, and bioinformatics analysis. The results suggested that increased co-expression of SATB2-AS1 and SATB2 was significantly associated with poor overall survival (OS) and relapse-free survival (RFS), and was a biomarker for risk stratification in patients with osteosarcoma. Mechanistically, SATB2-AS1 promotes tumor growth and lung metastasis by regulating SATB2 in vivo. SATB2-AS1 directly binds to POU3F1 for mediating SATB2 expression in MNNG/HOS cells. In addition, SATB2-AS1 and SATB2 might be potential immunomodulators for negatively affecting immune cell infiltration by the IL-17 signaling pathway. In summary, SATB2-AS1 promoted tumor cell growth and lung metastasis by activating SATB2, thereby associated with poor prognosis in patients with osteosarcoma, which indicated that SATB2-AS1 and SATB2 might be novel biomarkers for risk stratification and promising therapeutic targets for osteosarcoma.

Published in Journal of Bone Oncology

ISSN: 2212-1374 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Diseases of the musculoskeletal system; Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: http://www.journals.elsevier.com/journal-of-bone-oncology/

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