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RNA干扰介导的MCM7基因敲低对慢性粒细胞白血病细胞的作用及其对白血病的治疗潜力。

RNAi-mediated knockdown of MCM7 gene on CML cells and its therapeutic potential for leukemia.

作者信息

Tian Liang, Liu Juan, Xia Guo-Hua, Chen Bao-An

机构信息

Department of Hematology and Oncology, Medical School, Zhongda Hospital, Southeast University, 87 Dingjiaqiao, Nanjing, 210009, China.

Department of Digestive System, Medical School, Zhongda Hospital, Southeast University, Nanjing, China.

出版信息

Med Oncol. 2017 Feb;34(2):21. doi: 10.1007/s12032-016-0878-x. Epub 2017 Jan 5.

Abstract

MCM7 is one of the subunits of MCM2-7 complex, which is essential to DNA replication licensing and the control of cell cycle progression. It has been demonstrated that MCM7 participates in mRNA transcription and DNA damage regulation as well. MCM7 gene is found to be over-expressed in multiple cancers, but there are few reports about its effect in leukemia. Recent studies have proven that MCM7 expression has a relationship with diagnosis and prognosis, which has led to their potential clinical application as a marker for cancer screening. RNA interference (RNAi) is a biological process in which RNA molecules inhibit gene expression, typically by causing the destruction of specific mRNA molecules. It is a valuable research tool, which is widely used in cell culture and living organisms as well as in medicine recent years. It is indicated that RNAi application for targeting functional carcinogenic molecules, tumor resistance to chemotherapy and radiotherapy is required in cancer treatment. Gene products knockdown by RNAi technology exerts anti-proliferative and pro-apoptotic effects upon cell culture systems, animal models and in clinical trials in the most studies. In the present study, we found that MCM7 highly expressed in K562 cells rather than that in normal neutrophils. Thus, lentivirus-mediated shRNA targeting MCM7 was used to suppress its endogenous expression in K562 cells and develop a novel therapeutic strategy for leukemia.

摘要

MCM7是MCM2-7复合体的亚基之一,对DNA复制许可和细胞周期进程的控制至关重要。已证明MCM7也参与mRNA转录和DNA损伤调节。研究发现MCM7基因在多种癌症中过表达,但关于其在白血病中的作用报道较少。最近的研究证实MCM7表达与诊断和预后有关,这使其作为癌症筛查标志物具有潜在的临床应用价值。RNA干扰(RNAi)是一种生物学过程,其中RNA分子抑制基因表达,通常是通过导致特定mRNA分子的破坏来实现。它是一种有价值的研究工具,近年来在细胞培养、生物体以及医学中都有广泛应用。有研究表明,在癌症治疗中需要应用RNAi靶向功能性致癌分子、肿瘤对化疗和放疗的抗性。在大多数研究中,通过RNAi技术敲低基因产物对细胞培养系统、动物模型以及临床试验都具有抗增殖和促凋亡作用。在本研究中,我们发现MCM7在K562细胞中高表达,而在正常中性粒细胞中不高表达。因此,利用慢病毒介导的靶向MCM7的短发夹RNA(shRNA)来抑制其在K562细胞中的内源性表达,并开发一种新的白血病治疗策略。

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