COPB2作为人骨肉瘤细胞生长的关键调节因子：潜在的治疗靶点和预后指标

IF 3.5 2区医学 Q2 Medicine

Journal of Bone Oncology Pub Date : 2025-07-12 DOI:10.1016/j.jbo.2025.100702

Yunpeng Cui , Xuedong Shi , Qiwei Wang , Wence Wu , Yuanxing Pan , Bing Wang , Mingxing Lei

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引用次数: 0

摘要

cocoatomer protein complex subunit beta 2 （COPB2）是cocoatomer protein complex I的重要组成部分，负责囊泡运输。既往研究表明，COPB2在恶性肿瘤中高表达，参与细胞增殖和凋亡。然而，COPB2在骨肉瘤中的作用及其潜在机制尚不清楚。本研究旨在探讨COPB2对人骨肉瘤细胞增殖、凋亡和集落形成的影响，并探讨其可能的机制。方法利用癌症基因组图谱（TCGA）数据库的数据进行kaplan - meier生存分析，评估COPB2表达与骨肉瘤患者预后的关系。此外，利用免疫组织化学和定量实时PCR （qRT-PCR）检测COPB2在骨肉瘤组织样本和四种骨肉瘤细胞系中的表达。在U2OS和SAOS-2人骨肉瘤细胞中，利用siRNA下调COPB2的表达。细胞组学/Celigo和Giemsa染色分别评估细胞增殖和集落形成。流式细胞术检测细胞周期分布及凋亡情况。在体内模型中评估肿瘤生长情况。此外，利用Human Phospho-Kinase Array Kit研究COPB2对骨肉瘤细胞的调控机制。结果COPB2高表达患者的总生存期和无病生存期均短于COPB2低表达患者。发现COPB2在骨肉瘤组织样本和细胞系中高度表达。沉默COPB2可显著抑制细胞增殖和集落形成。此外，COPB2沉默改变了细胞周期分布，导致细胞周期阻滞在G2期，促进骨肉瘤细胞凋亡。进一步研究发现，COPB2沉默在体内抑制骨肉瘤细胞的肿瘤生长和肺转移，其对细胞增殖和凋亡的影响可能是通过调节激酶磷酸化水平介导的。结论scopb2在骨肉瘤细胞中表达升高，在骨肉瘤细胞生长调控中起重要作用。沉默COPB2可抑制细胞增殖、集落形成并促进细胞凋亡。此外，COPB2沉默在体内抑制肿瘤生长，这表明它有可能成为治疗骨肉瘤的重要治疗靶点。

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COPB2 as a key regulator of cell growth in human osteosarcoma cells: Potential therapeutic target and prognostic indicator

Purpose

Coatomer protein complex subunit beta 2 (COPB2) is a crucial component of the coatomer protein complex I, responsible for vesicle transport. Previous studies have indicated that COPB2 is highly expressed in malignant tumors and is involved in cell proliferation and apoptosis. However, the role of COPB2 in osteosarcoma and its underlying mechanisms remain unclear. This study aimed to investigate the impact of COPB2 on proliferation, apoptosis, and colony formation in human osteosarcoma cells, as well as to explore potential mechanisms.

Methods

Kaplan-Meier survival analysis was conducted to assess the association between COPB2 expression and the prognosis of osteosarcoma patients using data extracted from the Cancer Genome Atlas (TCGA) database. Additionally, COPB2 expression was examined in osteosarcoma tissue samples and four osteosarcoma cell lines using immunohistochemistry and quantitative real-time PCR (qRT-PCR). COPB2 expression was downregulated using siRNA in U2OS and SAOS-2 human osteosarcoma cells. Cell proliferation and colony formation were assessed using Cellomics/Celigo and Giemsa staining, respectively. Flow cytometry was used to evaluate cell cycle distribution and apoptosis. Tumor growth was evaluated in vivo model. Furthermore, the regulation mechanism of COPB2 on osteosarcoma cells was investigated using the Human Phospho-Kinase Array Kit.

Results

Patients with high COPB2 expression exhibited shorter overall survival and disease-free survival compared to those with low COPB2 expression. COPB2 was found to be highly expressed in osteosarcoma tissue samples and cell lines. Silencing of COPB2 significantly inhibited cell proliferation and colony formation. Additionally, COPB2 silencing altered the cell cycle distribution, leading to cell cycle arrest in the G2 phase, and promoted cell apoptosis in osteosarcoma cells. Further investigations revealed that COPB2 silencing inhibited tumor growth and lung metastases of osteosarcoma cells in vivo, and its effects on cell proliferation and apoptosis may be mediated through the regulation of kinase phosphorylation levels.

Conclusions

COPB2 expression is increased in osteosarcoma cells and plays a crucial role in cell growth regulation. Silencing of COPB2 inhibits cell proliferation, colony formation, and promotes cell apoptosis. Furthermore, COPB2 silencing inhibits tumor growth in vivo, suggesting its potential as an important therapeutic target in treating 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.