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