磷酸酶CTDSPL2促进骨肉瘤的增殖、侵袭、转移和瑞非尼耐药

IF 3.4 2区医学 Q2 Medicine

Journal of Bone Oncology Pub Date : 2025-04-26 DOI:10.1016/j.jbo.2025.100684

Guannan Bai , Shaobo Zhao , Manli Zhao , Limiao Chen , Wenhao Chen

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引用次数: 0

摘要

骨肉瘤是儿童和青少年中最常见的骨恶性肿瘤。转移性和复发性骨肉瘤患者预后较差。瑞非尼是一种多激酶抑制剂，推荐作为晚期骨肉瘤治疗标准化疗的补充。与瑞非尼耐药相关的机制尚不清楚。在这项研究中，我们使用regorafenib处理的骨肉瘤细胞系（MG-63， HOS-MNNG用于转录组学，HOS-MNNG用于蛋白质组学和磷酸化蛋白质组学）进行转录组学、蛋白质组学和磷酸化蛋白质组学研究。通过对差异表达基因的综合多组学和验证分析，鉴定出骨肉瘤细胞恶性肿瘤的必要基因。研究了必需基因对骨肉瘤增殖、侵袭和迁移的影响。该研究还评估了它们在骨肉瘤细胞凋亡中的作用。通过免疫组化检测必需基因的上调。通过综合多组学和验证分析，我们发现CTDSPL2基因可能在骨肉瘤的恶性和瑞非尼耐药中发挥作用。体外和临床标本实验表明，CTDSPL2促进骨肉瘤细胞的增殖、侵袭和转移，同时抑制肿瘤细胞凋亡。综上所述，CTDSPL2是骨肉瘤细胞存活的重要基因。下调CTDSPL2表达可显著抑制骨肉瘤细胞的增殖、侵袭和转移，提示其参与骨肉瘤肿瘤的形成和发展。我们的数据显示CTDSPL2是骨肉瘤患者的潜在治疗靶点。

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The phosphatase CTDSPL2 promotes proliferation, invasion, metastasis and regorafenib resistance in osteosarcoma

Osteosarcoma is the most common bone malignancy in children and adolescents. Patients with metastatic and recurrent osteosarcoma have poor prognosis. Regorafenib is a multi-kinase inhibitor recommended as a complement to standard chemotherapy in the treatment of advanced osteosarcoma. The mechanisms associated with regorafenib resistance remains unclear.

In this study we performed transcriptomics, proteomics and phosphorylated proteomics using regorafenib-treated osteosarcoma cell lines (MG-63, HOS-MNNG for transcriptomics, HOS-MNNG for proteomics and phosphorylated proteomics). After comprehensive multiomics and verification analyses of differentially expressed genes, essential genes for the malignancy of osteosarcoma cells were identified. The effects of essential genes on the proliferation, invasion, and migration of osteosarcoma were determined. The study also evaluated their role in the apoptosis of osteosarcoma cells. The up-regulation of essential genes was determined by immunohistochemistry assays.

Using comprehensive multiomics and verification analyses we found that the CTDSPL2 gene might play a role in the malignancy and Regorafenib resistance in osteosarcoma. In vitro and clinical specimen assays demonstrated that CTDSPL2 promotes the proliferation, invasion and metastasis of osteosarcoma cells, while inhibiting tumor cell apoptosis.

In conclusion CTDSPL2 was identified as an essential gene for survival of osteosarcoma cells. Knockdown of CTDSPL2 expression significantly inhibited the proliferation, invasion, and metastasis of osteosarcoma cells, suggesting that it is involved in the formation and development of osteosarcoma tumors. Our data showed that CTDSPL2 is a potential therapeutic target for patients with osteosarcoma.

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来源期刊

Journal of Bone Oncology ONCOLOGY-

CiteScore

7.20

自引率

2.90%

发文量

审稿时长

34 days

期刊介绍： The Journal of Bone Oncology is a peer-reviewed international journal aimed at presenting basic, translational and clinical high-quality research related to bone and cancer. As the first journal dedicated to cancer induced bone diseases, JBO welcomes original research articles, review articles, editorials and opinion pieces. Case reports will only be considered in exceptional circumstances and only when accompanied by a comprehensive review of the subject. The areas covered by the journal include: Bone metastases (pathophysiology, epidemiology, diagnostics, clinical features, prevention, treatment) Preclinical models of metastasis Bone microenvironment in cancer (stem cell, bone cell and cancer interactions) Bone targeted therapy (pharmacology, therapeutic targets, drug development, clinical trials, side-effects, outcome research, health economics) Cancer treatment induced bone loss (epidemiology, pathophysiology, prevention and management) Bone imaging (clinical and animal, skeletal interventional radiology) Bone biomarkers (clinical and translational applications) Radiotherapy and radio-isotopes Skeletal complications Bone pain (mechanisms and management) Orthopaedic cancer surgery Primary bone tumours Clinical guidelines Multidisciplinary care Keywords: bisphosphonate, bone, breast cancer, cancer, CTIBL, denosumab, metastasis, myeloma, osteoblast, osteoclast, osteooncology, osteo-oncology, prostate cancer, skeleton, tumour.