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FKBP11 可改善骨肉瘤细胞的恶性程度,并可作为骨肉瘤的预后因素。

FKBP11 improves the malignant property of osteosarcoma cells and acts as a prognostic factor of osteosarcoma.

机构信息

Jiangxi Key Laboratory of Cancer Metastasis and Precision Treatment, Central Laboratory, The First Hospital of Nanchang, The Third Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330008, P.R. China.

Department of Orthopedics, The First Hospital of Nanchang, The Third Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330008, P.R. China.

出版信息

Aging (Albany NY). 2023 Apr 1;15(7):2450-2459. doi: 10.18632/aging.204523.

Abstract

BACKGROUND

Osteosarcoma has become the most common bone malignancy in adolescents. Although the clinical treatment of osteosarcoma has advanced considerably in recent years, the 5-year survival rate has not improved significantly. Recently, many studies have shown that mRNA has unique advantages as a target for drug therapy. Therefore, this study aimed to identify a new prognostic factor and provide a new target for the treatment of osteosarcoma to improve the prognosis of patients.

METHODS AND RESULTS

We selected prognostic genes that are closely associated with osteosarcoma clinical features by obtaining osteosarcoma patient information from the GTEx and TARGET databases, and then we developed a risk model. We detected the expression of FKBP11 in osteosarcoma by qRT-PCR, western blotting, and immunohistochemistry and performed CCK-8, Transwell, colony formation, and flow cytometry assays to reveal the regulatory role of FKBP11. We found that FKBP11 was highly expressed in osteosarcoma; silencing FKBP11 expression suppressed the invasion and migration of osteosarcoma cells, slowed cell proliferation, and promoted apoptosis. We also found that silencing the expression of FKBP11 led to inhibition of MEK/ERK phosphorylation.

CONCLUSIONS

In conclusion, we validated that the prognostic factor FKBP11 is closely associated with osteosarcoma. Additionally, we identified a novel mechanism by which FKBP11 ameliorates the malignant properties of osteosarcoma cells through the MAPK pathway and serves as a prognostic factor in osteosarcoma. This study provides a new method for the treatment of osteosarcoma.

摘要

背景

骨肉瘤已成为青少年中最常见的骨恶性肿瘤。尽管近年来骨肉瘤的临床治疗有了显著进展,但 5 年生存率并未显著提高。最近,许多研究表明,mRNA 作为药物治疗的靶点具有独特的优势。因此,本研究旨在确定新的预后因素,并为骨肉瘤的治疗提供新的靶点,以改善患者的预后。

方法和结果

我们通过从 GTEx 和 TARGET 数据库中获取骨肉瘤患者信息,选择与骨肉瘤临床特征密切相关的预后基因,并构建风险模型。我们通过 qRT-PCR、western blot 和免疫组化检测骨肉瘤中 FKBP11 的表达,并进行 CCK-8、Transwell、集落形成和流式细胞术实验以揭示 FKBP11 的调节作用。我们发现 FKBP11 在骨肉瘤中高表达;沉默 FKBP11 表达可抑制骨肉瘤细胞的侵袭和迁移,减缓细胞增殖并促进细胞凋亡。我们还发现沉默 FKBP11 的表达可抑制 MEK/ERK 磷酸化。

结论

综上所述,我们验证了预后因子 FKBP11 与骨肉瘤密切相关。此外,我们还确定了 FKBP11 通过 MAPK 通路改善骨肉瘤细胞恶性特性并作为骨肉瘤预后因素的新机制。本研究为骨肉瘤的治疗提供了新方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a10/10120909/0597c1d85ea7/aging-15-204523-g001.jpg

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