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多种癌症中守护蛋白1的表达:一种潜在的治疗靶点

Shugoshin 1 expression in various cancers: a potential target for therapy.

作者信息

Ankathatti Narayanaswamy Indumathi, Kattepur Abhay Kumaraswamy, Raju Kalyani, Perumal Venkatachalam, Ramalingam Ravi, Raavi Venkateswarlu

机构信息

Department of Cell Biology and Molecular Genetics, Sri Devaraj Urs Academy of Higher Education and Research (Deemed to be University), Kolar, Karnataka, 563 103, India.

Department of Surgical Oncology, R L Jalappa Institute of Oncology, Sri Devaraj Urs Academy of Higher Education and Research (Deemed to be University), Kolar, Karnataka, 563 103, India.

出版信息

Clin Transl Oncol. 2025 May;27(5):1953-1966. doi: 10.1007/s12094-024-03749-1. Epub 2024 Oct 30.

Abstract

Shugoshin 1 (SGO1) is one of the Shugoshin (guardian spirit) family proteins, which is reported to be majorly involved in the protection of centromeres and proper segregation of chromosomes during cell division. Recent studies found that the altered expression of SGO1 is associated with various cancers and genetic disorders, and suggested as a target for therapy. In the present study, we have reviewed the available literature on SGO1 gene and protein expression in various cancer-cell lines, animal models and cancer patients, and targeting SGO1 with siRNA/shRNA. A significant increase in the expression of SGO1 mRNA and protein levels were observed in prostate, renal, lung, breast, neuroblastoma, leukemia, hepatocellular, and colon cancer-cell lines and the levels were associated with increased cellular proliferation, invasion, and metastasis. The altered SGO1 levels were observed in SGO1 knockout/haploinsufficient mice compared to wild type and the levels were associated with increased chromosome instability and tumorigenesis. Consistent with cell lines, higher SGO1 expression was also observed in tumor tissues of cancer patients compared to adjacent normal tissue and the levels were positively correlated with tumor stage, grade, size, and hormonal status. Higher SGO1 expression was related to resistance to chemotherapeutic agents and the knockdown of SGO1 increased sensitivity to those agents. Furthermore, targeting SGO1 with siRNA/shRNA reduced the expression of SGO1 and proliferation, and induced apoptosis of cancer cells. Overall, the SGO1 expression levels were significantly higher in various cancers, and targeting SGO1 with siRNA and shRNA reduced the levels of SGO1, proliferation and metastasis of cancers.

摘要

守护蛋白1(SGO1)是守护蛋白家族的蛋白质之一,据报道其主要参与在细胞分裂过程中保护着丝粒和确保染色体正确分离。最近的研究发现,SGO1表达改变与多种癌症和遗传疾病相关,并被建议作为治疗靶点。在本研究中,我们综述了关于SGO1基因和蛋白在各种癌细胞系、动物模型及癌症患者中的表达情况,以及用小干扰RNA(siRNA)/短发夹RNA(shRNA)靶向作用于SGO1的相关文献。在前列腺癌、肾癌、肺癌、乳腺癌、神经母细胞瘤、白血病、肝癌和结肠癌细胞系中观察到SGO1信使核糖核酸(mRNA)和蛋白水平显著升高,且这些水平与细胞增殖、侵袭和转移增加相关。与野生型相比,在SGO1基因敲除/单倍体不足的小鼠中观察到SGO1水平改变,且这些水平与染色体不稳定性增加和肿瘤发生相关。与细胞系情况一致,与相邻正常组织相比,在癌症患者的肿瘤组织中也观察到较高的SGO1表达,且这些水平与肿瘤分期、分级、大小和激素状态呈正相关。较高的SGO1表达与对化疗药物的耐药性相关,而敲低SGO1可增加对这些药物的敏感性。此外,用siRNA/shRNA靶向作用于SGO1可降低SGO1的表达及细胞增殖,并诱导癌细胞凋亡。总体而言,SGO1在各种癌症中的表达水平显著更高,用siRNA和shRNA靶向作用于SGO1可降低SGO1水平、癌症的增殖和转移。

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