Long intergenic non-coding RNA DIO3OS promotes osteosarcoma metastasis via activation of the TGF-β signaling pathway: a potential diagnostic and immunotherapeutic target for osteosarcoma

Cancer Cell International

Research

Zhao Yuan¹  Jia Guo²  Jiahao Liu³  Zhiwen Wu³  Zhi Du³  Xiaokun Zhao³  Jian Zhang³  Qi Chen³  Jingyu Jia⁴  Xigao Cheng⁴  Jinghong Yuan⁴  Tianlong Wu⁴ 

[1] Clinical Research Center, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China;Department of Orthopaedics, Jiangxi Provincial People’s Hospital Affiliated to Nanchang University, Nanchang, Jiangxi, China;Department of Orthopaedics, The Second Affiliated Hospital of Nanchang University, Nanchang, 1 Minde Road, Donghu, 330006, Nanchang, Jiangxi, People’s Republic of China;Department of Orthopaedics, The Second Affiliated Hospital of Nanchang University, Nanchang, 1 Minde Road, Donghu, 330006, Nanchang, Jiangxi, People’s Republic of China;Institute of Orthopaedics of Jiangxi Province, Nanchang, Jiangxi, China;Institute of Minimally Invasive Orthopaedics of Nanchang University, Nanchang University, Nanchang, Jiangxi, China;

关键词: Osteosarcoma;    DIO3OS;    TGF-β signaling pathway;    Immunotherapy;    Diagnosis;   

DOI  :  10.1186/s12935-023-03076-5

 received in 2022-08-01, accepted in 2023-09-20,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundThe aim of this study was to determine the underlying potential mechanisms and function of DIO3OS, a lincRNA in osteosarcoma and clarify that DIO3OS can be used as a potential diagnostic biomarker and immunotherapeutic target.MethodsThe expression matrix data and clinical information were obtained from XENA platform of UCSC and GEO database as the test cohorts. The external validation cohort was collected from our hospital. Bioinformatics analysis was used to annotate the biological function of DIO3OS. Immune infiltration and immune checkpoint analysis were applied to evaluate whether DIO3OS can be used as an immunotherapeutic target. ROC curves and AUC were established to assess the diagnostic value of DIO3OS for differentiating patients from other subtypes sarcoma. The expression analysis was detected by qRT-PCR, western blot, and immunohistochemical. Wound healing assay and Transwell assay were applied to determine the migration and invasion function of DIO3OS in osteosarcoma cell lines. The tail vein injection osteosarcoma cells metastases model was used in this research.ResultsHigh expression of DIO3OS was identified as a risk lincRNA for predicting overall survival of osteosarcoma in test cohort. The outcomes of experiments in vitro and in vivo showed that low expression of DIO3OS limited osteosarcoma tumor metastasis with inhibiting TGF-β signaling pathway. Immune checkpoint genes (CD200 and TNFRSF25) expressions were inhibited in the low DIO3OS expression group. The DIO3OS expression can be applied to reliably distinguish osteosarcoma from lipomatous neoplasms, myomatous neoplasms, nerve sheath tumors, and synovial-like neoplasms. This result was further validated in the validation cohort.ConclusionsIn conclusion, our outcomes indicated that DIO3OS is a potential diagnostic and prognostic biomarker of osteosarcoma, emphasizing its potential as a target of immunotherapy to improve the treatment of osteosarcoma through TGF-β signaling pathway.Trial registration number: The present retrospectively study was approved by the Ethics Committee of The Second Affiliated Hospital of Nanchang University [Review (2020) No. (115)].

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023

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