Identification and experimental validation of Stearoyl-CoA desaturase is a new drug therapeutic target for osteosarcoma

Jiangbo Nie; Cheng He; Zhiguo Shu; Ning Liu; Yanxin Zhong; Xinhua Long; Jiaming Liu; Feng Yang; Zhili Liu; Ping Huang

doi:10.1016/j.ejphar.2023.176249

Identification and experimental validation of Stearoyl-CoA desaturase is a new drug therapeutic target for osteosarcoma

Eur J Pharmacol. 2024 Jan 15:963:176249. doi: 10.1016/j.ejphar.2023.176249. Epub 2023 Dec 7.

Authors

Jiangbo Nie¹, Cheng He², Zhiguo Shu¹, Ning Liu¹, Yanxin Zhong¹, Xinhua Long³, Jiaming Liu¹, Feng Yang¹, Zhili Liu⁴, Ping Huang⁵

Affiliations

¹ Department of Orthopedic Surgery, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China; Institute of Spine and Spinal Cord, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China; Medical Innovation Center, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China.
² Department of Orthopedics, The 908th Hospital of Chinese People's Liberation Army Joint Logistic Support Force, Nanchang, China.
³ Institute of Spine and Spinal Cord, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China; Medical Innovation Center, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China.
⁴ Department of Orthopedic Surgery, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China; Institute of Spine and Spinal Cord, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China; Medical Innovation Center, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China. Electronic address: zhili-liu@ncu.edu.cn.
⁵ Institute of Spine and Spinal Cord, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China; Medical Innovation Center, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China; Department of Nutrition, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China. Electronic address: ndyfy03260@ncu.edu.cn.

PMID: 38070637
DOI: 10.1016/j.ejphar.2023.176249

Abstract

Osteosarcoma (OS) is the most common malignant bone tumor. Fatty acid reprogramming plays an essential role in OS progression. However, new fatty acid related therapeutic targets of OS have not been completely elucidated. Therefore, we firstly identified 113 differentially expressed fatty acid metabolism genes using bioinformatic analysis, 19 of which were found to be associated with OS prognosis. Then, 7 hub genes were screened out and yielded a strong prediction accuracy (AUC value = 0.88, at 3 years) for predicting the survival status of OS patients. Furthermore, we confirmed that SCD was highly expressed in OS cells and patients. And Knock-down of SCD impaired proliferation and migration of OS cells. Moreover, SCD was transcriptionally activated by c-Myc to promote proliferation and migration of OS cells. Finally, SCD inhibitor could significantly induce OS ferroptosis in vitro and in vivo. In conclusion, we identified that SCD was a reliable risk factor for OS patients. And SCD was activated by c-Myc. The inhibitor of SCD could significantly impaired OS growth and induce OS ferroptosis, which indicated that SCD was a potential drug target for OS treatment.

Keywords: Drug therapeutic target; Fatty acid metabolism; Osteosarcoma; SCD; c-Myc.

MeSH terms

Fatty Acids / metabolism
Humans
Osteosarcoma* / drug therapy
Osteosarcoma* / genetics
Stearoyl-CoA Desaturase* / genetics
Stearoyl-CoA Desaturase* / metabolism

Substances

Stearoyl-CoA Desaturase
Fatty Acids