Wang Lei, Xu Man-Li, Wang Chang, Dong Qing-Qing, Miao Zhi, Chen Xiao-Ying, Wang Nan, He Hong-Peng, Zhang Tong-Cun, Luo Xue-Gang
Key Laboratory of Industrial Fermentation Microbiology, Tianjin University of Science and Technology, Ministry of Education, Tianjin 300457, P.R. China.
Tianjin Key Laboratory of Industrial Microbiology, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, P.R. China.
Oncol Lett. 2020 May;19(5):3469-3476. doi: 10.3892/ol.2020.11465. Epub 2020 Mar 19.
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.
顺铂耐药一直是限制其作为化疗药物临床应用的主要因素。本研究旨在探讨与肿瘤密切相关的组蛋白甲基转移酶SET和MYND结构域包含蛋白3（SMYD3）是否会影响肿瘤对顺铂化疗的敏感性。采用实时定量聚合酶链反应、蛋白质免疫印迹法、荧光素酶报告基因检测法、MTT法和克隆形成试验来检测SMYD3对顺铂化疗能力的影响。在本研究中，SMYD3在MCF-7和T47D乳腺癌细胞中呈现出不同的表达模式。此外，这种差异表达与肿瘤细胞对顺铂的耐药性相关。此外，小干扰RNA转染后敲低SMYD3可增加顺铂敏感性，而SMYD3过表达则降低顺铂敏感性。此外，敲低SMYD3可协同增强顺铂诱导的细胞凋亡。顺铂处理期间SMYD3表达下调。此外，SMYD3 3'-非翻译区的转录调控活性也下调。这些结果表明，SMYD3可能影响细胞对顺铂的敏感性并参与顺铂耐药的发生发展，这一过程可能涉及微小RNA-124介导的调控。
