The role of Notch ligand Jagged1 in osteosarcoma proliferation, metastasis, and recurrence.

The role of Notch ligand Jagged1 in osteosarcoma proliferation, metastasis, and recurrence.
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Notch配体Jagged1在骨肉瘤增殖、转移和复发中的作用。

DOI:
10.1186/s13018-021-02372-y
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发表时间:
2021-03-29
影响因子:
2.6
通讯作者:
Xu Y
Xu Y
中科院分区:
医学3区
文献类型:
--
作者:
Zhang J;Li N;Lu S;Chen Y;Shan L;Zhao X;Xu Y

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骨肉瘤是年轻人最常见的原发性骨癌,由于高转移复发和耐药,转移性骨肉瘤患者的5年生存率低于30%。Notch是一种在进化过程中高度保守的细胞间信号传导途径,Jagged1是Notch的重要配体。虽然有研究发现Notch受体和配体包括Jagged1在骨肉瘤组织和细胞中高表达,但Jagged1在骨肉瘤进展和转移中的作用尚不清楚。收集68例患者的肿瘤组织,采用免疫组织化学染色对这些患者进行Jagged 1表达分组。实时定量PCR和Western blotting检测Jagged1的表达。我们用siRNA敲低F5M2细胞中Jagged1的表达。采用集落形成实验和MTT法检测Jagged1基因敲除前后F5M2细胞的增殖情况。Transwell法检测F5M2细胞的迁移和侵袭能力。在本研究中,我们发现Jagged 1的高表达与68例骨肉瘤的转移和复发密切相关。Jagged1在高转移的F5M2细胞中的表达明显高于低转移的F4细胞。敲低Jagged1基因可降低F5M2细胞的增殖、迁移和侵袭能力。Jagged1的高表达与骨肉瘤的转移和复发密切相关。敲除Jagged1可显著降低骨肉瘤细胞的增殖、迁移和侵袭。我们的研究结果表明,敲低Jagged1可能是一种潜在的有效治疗转移性骨肉瘤。
Osteosarcoma is the most common primary bone cancer occurring in young adults and the 5-year survival rate of patients with metastatic osteosarcoma is less than 30% due to high metastatic recurrence and drug resistance. Notch is a highly conserved cell to cell signaling pathway in evolution, and Jagged1 is an important ligand of Notch. Although some studies have found that Notch receptors and ligands including Jagged1 were highly expressed in osteosarcoma tissues and osteosarcoma cells, the role of Jagged1 in osteosarcoma progression and metastasis are still not clear. Tumor tissues were collected from 68 patients and immunohistochemical staining was employed to group these patients by expression of Jagged1. Real-time quantitative PCR and Western blotting were used to detect the expression of Jagged1. We used siRNA to knockdown the expression of Jagged1 in F5M2 cells. Colony formation assay and MTT were employed to detect and analyze the proliferation of F5M2 cells with or without knockdown of Jagged1. Transwell assay were used to detect the migration and invasion of F5M2 cells. In this study, we found that the high expression of Jagged1 is closely related to the metastasis and recurrence of osteosarcoma in 68 clinical specimens. The expression of Jagged1 in F5M2 cells with high metastasis was significantly higher than that in F4 cells with low metastasis. Knockdown of Jagged1 led to lower ability of proliferation, migration, and invasion in F5M2 cells. The high expression of Jagged1 is closely related to the metastasis and recurrence of osteosarcoma. Knockdown of Jagged1 significantly reduced the proliferation, migration, and invasion of osteosarcoma cells. Our results suggested that knockdown of Jagged1 may be a potentially effective treatment for metastatic osteosarcoma.
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