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

长链间非编码 RNA DIO3OS 通过激活 TGF-β 信号通路促进骨肉瘤转移:骨肉瘤的潜在诊断和免疫治疗靶点

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作者:Jinghong Yuan, Jingyu Jia, Tianlong Wu, Zhi Du, Qi Chen, Jian Zhang, Zhiwen Wu, Zhao Yuan, Xiaokun Zhao, Jiahao Liu, Jia Guo, Xigao Cheng

Background

The

Conclusions

In 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.

Methods

The 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.

Results

High 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. Conclusions: In

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