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SET and MYND domain-containing protein 3 inhibits tumor cell sensitivity to cisplatin

机译:含有Mynd含有域的蛋白质3抑制肿瘤细胞对顺铂的敏感性

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摘要

Cisplatin resistance has been a major factor limiting its clinical use as a chemotherapy drug. The present study aimed to investigate whether SET and MYND domain-containing protein 3 (SMYD3), a histone methyltransferase closely associated with tumors can affect the sensitivity of tumors to cisplatin chemotherapy. Real time-qPCR, western blotting, the luciferase reporter, MTT and clonogenic assays were performed to detect the effects of SMYD3 on the chemotherapy capacity of cisplatin. In the present study, SMYD3 exhibited different expression patterns in MCF-7 and T47D breast cancer cells. In addition, this differential expression was associated with tumor cell resistance to cisplatin. Furthermore, SMYD3 knockdown following small interfering RNA transfection increased cisplatin sensitivity, whereas SMYD3 overexpression decreased cisplatin sensitivity. In addition, SMYD3 knockdown synergistically enhanced cisplatin-induced cell apoptosis. SMYD3 expression was downregulated during cisplatin treatment. In addition, transcriptional regulatory activities of SMYD3 3 '-untranslated region were also downregulated. These results suggested that SMYD3 may affect cell sensitivity to cisplatin and participate in the development of cisplatin resistance, which is a process that may involve microRNA-124-mediated regulation.
机译:顺铂抗性是限制其临床用作化疗药物的主要因素。目前的研究旨在研究与肿瘤密切相关的组甲基转移酶是否探讨了是否含有MYND结构域的蛋白质3(SMYD3),可以影响肿瘤对顺铂化疗的敏感性。进行实时QPCR,Western印迹,荧光素酶报告,MTT和克隆纤维酶报告,检测SMYD3对顺铂化疗能力的影响。在本研究中,SMYD3在MCF-7和T47D乳腺癌细胞中表现出不同的表达模式。此外,这种差异表达与对顺铂的肿瘤细胞抗性有关。此外,在小干扰RNA转染后,SMYD3敲除增加了顺铂敏感性,而SMYD3过表达降低顺铂敏感性。此外,SMYD3敲低协同增强的顺铂诱导的细胞凋亡。在顺铂治疗过程中下调SMYD3表达。此外,SMYD3 3'-unlralstated地区的转录调节活动也在下调。这些结果表明SMYD3可能影响对顺铂的细胞敏感性,并参与顺铂抗性的发展,这是一种可能涉及MicroRNA-124介导的调节的过程。

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