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BUB1是一种在肉瘤中过表达的激酶:为骨肉瘤、脂肪肉瘤、滑膜肉瘤和平滑肌肉瘤寻找新的靶向治疗方法。

BUB1 an Overexpressed Kinase in Sarcoma: Finding New Target Therapy for Osteosarcoma, Liposarcoma, Synovial Sarcoma, and Leiomyosarcoma.

作者信息

Olvera-Valencia Mercedes, Luna-Maldonado Fernando, Juarez-Reyes Joselyn, Lopez-Saavedra Alejandro, Coronel-Hernandez Jossimar, Millan-Catalan Oliver, Guzman-Gomez Daniel, Rodríguez-Izquierdo Frida, Herrera Luis A, Cantú-De León David Francisco, Perez-Plasencia Carlos, Pérez-Yepez Eloy-Andres

机构信息

Programa Institucional de Biomedicina Molecular, Escuela Nacional de Medicina y Homeopatía del IPN, Guillermo Massieu Helguera #239 Fracc. La escalera, Ticoman 07320, Ciudad de Mexico, Mexico.

Laboratorio de Genómica, Instituto Nacional de Cancerología, San Fernando 22. Col. Sección XVI, Tlalpan 14080, Ciudad de Mexico, Mexico.

出版信息

Biomolecules. 2025 Jul 18;15(7):1046. doi: 10.3390/biom15071046.

DOI:10.3390/biom15071046
PMID:40723917
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12293735/
Abstract

Sarcomas are heterogeneous mesenchymal tumors, and their pharmacological treatment remains challenging due to the high toxicity and poor efficacy of current therapies. This study aimed to identify common overexpressed kinases in the four most frequent sarcoma subtypes to establish novel therapeutic targets. A bioinformatics approach using patient-derived gene expression data sets identified overexpressed kinases shared across these sarcoma types. Later, was determined as the kinase consistently overexpressed across the osteosarcoma, liposarcoma, leiomyosarcoma, and synovial sarcoma. Moreover, the role of this kinase was further validated through molecular and functional assays, including pharmacological inhibition in cell lines derived from the four sarcoma subtypes. BUB1 inhibition reduced the phosphorylation of AKT and H2A proteins, precluded cell proliferation, and inhibited colony formation in sarcoma cells. Finally, overall survival analysis highlighted a strong correlation between high expression and poorer survival rates in sarcoma patients. Altogether, these findings underscore the potential of BUB1 as a therapeutic target and prognostic marker in sarcomas. Targeted inhibition of BUB1 may provide a novel strategy to reduce tumor growth and improve outcomes for patients with bone and soft tissue sarcomas.

摘要

肉瘤是异质性间充质肿瘤,由于当前治疗方法的高毒性和低疗效,其药物治疗仍然具有挑战性。本研究旨在确定四种最常见肉瘤亚型中共同过度表达的激酶,以建立新的治疗靶点。一种使用患者来源基因表达数据集的生物信息学方法确定了这些肉瘤类型中共同过度表达的激酶。后来,确定为骨肉瘤、脂肪肉瘤、平滑肌肉瘤和滑膜肉瘤中持续过度表达的激酶。此外,通过分子和功能分析进一步验证了该激酶的作用,包括在源自四种肉瘤亚型的细胞系中进行药理学抑制。BUB1抑制降低了AKT和H2A蛋白的磷酸化,阻止了细胞增殖,并抑制了肉瘤细胞中的集落形成。最后,总生存分析突出了肉瘤患者中高表达与较差生存率之间的强相关性。总之,这些发现强调了BUB1作为肉瘤治疗靶点和预后标志物的潜力。对BUB1的靶向抑制可能为减少肿瘤生长和改善骨肉瘤和软组织肉瘤患者的预后提供一种新策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/51b5/12293735/ea82d43c1374/biomolecules-15-01046-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/51b5/12293735/f94321a0f44d/biomolecules-15-01046-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/51b5/12293735/ea82d43c1374/biomolecules-15-01046-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/51b5/12293735/f94321a0f44d/biomolecules-15-01046-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/51b5/12293735/ea82d43c1374/biomolecules-15-01046-g004.jpg

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本文引用的文献

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An R package for survival-based gene set enrichment analysis.一个用于基于生存的基因集富集分析的R包。
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BUB1 as a novel marker for predicting the immunotherapy efficacy and prognosis of breast cancer.BUB1作为预测乳腺癌免疫治疗疗效和预后的新型标志物。
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BUB1 induces AKT/mTOR pathway activity to promote EMT induction in human small cell lung cancer.BUB1 诱导 AKT/mTOR 通路活性促进人小细胞肺癌 EMT 诱导。
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BUB1 Promotes Gemcitabine Resistance in Pancreatic Cancer Cells by Inhibiting Ferroptosis.BUB1通过抑制铁死亡促进胰腺癌细胞对吉西他滨的耐药性。
Cancers (Basel). 2024 Apr 18;16(8):1540. doi: 10.3390/cancers16081540.
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Expression of the checkpoint kinase BUB1 is a predictor of response to cancer therapies.BUB1 检查点激酶的表达是癌症治疗反应的预测因子。
Sci Rep. 2024 Feb 23;14(1):4461. doi: 10.1038/s41598-024-55080-y.
7
Genomic profiling in GIST: Implications in clinical outcome and future challenges.胃肠间质瘤的基因组分析:对临床结果的影响和未来的挑战。
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Knockdown of BUB1 inhibits tumor necrosis factor-α-induced proliferation and migration of rheumatoid arthritis synovial fibroblasts by regulating PI3K/Akt pathway.BUB1 基因敲低通过调控 PI3K/Akt 通路抑制肿瘤坏死因子-α诱导的类风湿关节炎滑膜成纤维细胞的增殖和迁移。
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