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

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

doi:10.1186/s12935-023-03076-5

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 Int. 2023 Sep 26;23(1):215. doi: 10.1186/s12935-023-03076-5.

Authors

Jinghong Yuan^{1

2

3}, Jingyu Jia^{1

2

3}, Tianlong Wu^{1

2

3}, Zhi Du¹, Qi Chen¹, Jian Zhang¹, Zhiwen Wu¹, Zhao Yuan⁴, Xiaokun Zhao¹, Jiahao Liu¹, Jia Guo⁵, Xigao Cheng^{6

7

8}

Affiliations

¹ Department of Orthopaedics, The Second Affiliated Hospital of Nanchang University, Nanchang, 1 Minde Road, Donghu, Nanchang, 330006, Jiangxi, People's Republic of China.
² Institute of Orthopaedics of Jiangxi Province, Nanchang, Jiangxi, China.
³ Institute of Minimally Invasive Orthopaedics of Nanchang University, Nanchang University, Nanchang, Jiangxi, China.
⁴ Clinical Research Center, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
⁵ Department of Orthopaedics, Jiangxi Provincial People's Hospital Affiliated to Nanchang University, Nanchang, Jiangxi, China.
⁶ Department of Orthopaedics, The Second Affiliated Hospital of Nanchang University, Nanchang, 1 Minde Road, Donghu, Nanchang, 330006, Jiangxi, People's Republic of China. xigaocheng@hotmail.com.
⁷ Institute of Orthopaedics of Jiangxi Province, Nanchang, Jiangxi, China. xigaocheng@hotmail.com.
⁸ Institute of Minimally Invasive Orthopaedics of Nanchang University, Nanchang University, Nanchang, Jiangxi, China. xigaocheng@hotmail.com.

Abstract

Background: The 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.

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 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)].

Keywords: DIO3OS; Diagnosis; Immunotherapy; Osteosarcoma; TGF-β signaling pathway.

Abstract

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