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OCT4B1,一种新型的 OCT4 剪接变体,在胃癌中高表达,并发挥抗凋亡因子的作用。

OCT4B1, a novel spliced variant of OCT4, is highly expressed in gastric cancer and acts as an antiapoptotic factor.

机构信息

Department of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran.

出版信息

Int J Cancer. 2011 Jun 1;128(11):2645-52. doi: 10.1002/ijc.25643. Epub 2010 Nov 3.

Abstract

The octamer-binding transcription factor 4 (OCT4) is involved in regulating pluripotency and self-renewal maintenance of embryonic stem cells. Recently, misexpression of OCT4 has been also reported in some adult stem as well as cancer cells; a finding which is still controversial. In addition to the previously described spliced variants of the gene (e.g., OCT4A and OCT4B), we have recently identified a novel variant of the gene, designated as OCT4-B1. In this study, we investigated a potential expression and function of OCT4B1 in a series of gastric cancer tissues and a gastric adenocarcinoma cell line, AGS. Using the Taqman real-time PCR approach, we have detected the expression of OCT4B1 in tumors with no or much lower expression in marginal samples of the same patients (p < 0.002). We have also analyzed the effects of OCT4B1 knock-down in AGS cell line treated with specific siRNA directed toward OCT4B1. Our data revealed that interfering with the expression of OCT4B1 caused profound changes in the morphology and cell cycle distribution of the cells. Furthermore, down-regulation of OCT4B1 significantly elevated the relative activity of caspase-3/caspase-7 and the rate of apoptosis in the cells (more than 30%). All together, our findings suggest that OCT4B1 has a potential role in tumorigenesis of gastric cancer and candidates the variant as a new tumor marker with potential value in diagnosis and treatment of gastric cancer.

摘要

八聚体结合转录因子 4(OCT4)参与调节胚胎干细胞的多能性和自我更新维持。最近,也有报道称 OCT4 在一些成体干细胞和癌细胞中异常表达;这一发现仍存在争议。除了先前描述的基因剪接变体(如 OCT4A 和 OCT4B)外,我们最近还鉴定了基因的一种新变体,命名为 OCT4-B1。在这项研究中,我们研究了 OCT4B1 在一系列胃癌组织和胃癌腺癌细胞系 AGS 中的潜在表达和功能。使用 Taqman 实时 PCR 方法,我们检测到 OCT4B1 在肿瘤中的表达,而在同一患者的边缘样本中表达水平较低或几乎没有(p<0.002)。我们还分析了针对 OCT4B1 的特异性 siRNA 处理 AGS 细胞系后 OCT4B1 敲低的影响。我们的数据显示,干扰 OCT4B1 的表达会导致细胞形态和细胞周期分布发生深刻变化。此外,下调 OCT4B1 显著增加了细胞中 caspase-3/caspase-7 的相对活性和细胞凋亡率(超过 30%)。总之,我们的研究结果表明,OCT4B1 在胃癌的发生中具有潜在作用,并将该变体候选为一种新的肿瘤标志物,具有在胃癌的诊断和治疗中潜在的应用价值。

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