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鼻咽癌潜在肿瘤抑制因子 NESG1 的蛋白质组学特征。

Proteomic features of potential tumor suppressor NESG1 in nasopharyngeal carcinoma.

机构信息

Department of Pathology, Basic School of Guangzhou Medical College, Guangzhou, China.

出版信息

Proteomics. 2012 Nov;12(22):3416-25. doi: 10.1002/pmic.201200146. Epub 2012 Oct 19.

Abstract

We previously defined the recently revised NESG1 gene as a potential tumor suppressor in nasopharyngeal carcinoma (NPC). Here, we further used proteomics technology to globally examine NESG1-controlled proteins in NPC cells. Twenty-six proteins were found to be deregulated by NESG1 using proteomics analysis while enolase 1 (alpha) (ENO1), heat shock protein 90 kDa beta (Grp94), member 1 (HSP90B1), and cathepsin D (CTSD) proteins were differentially expressed by Western blot. Interestingly, a-enolase (ENO1), an overexpressed gene in NPC, was confirmed as a NESG1-regulated protein in NPC cells. Overexpressed ENO1 not only restored cell proliferation and cell-cycle progression, but also antagonized the regulation of NESG1 to cell-cycle regulators p21 and CCNA1 expression as well as induced the expression of C-Myc, pRB, and E2F1 in NESG1-ovexpressed NPC cells. Real-time PCR and immunohistochemistry analysis showed that NESG1 expression is negatively correlated with ENO1 expression in NPC tissues. Our observations suggest that ENO1 downregulation plays an important role in NESG1-induced growth inhibition of NPC cancer cells.

摘要

我们之前将最近修订的 NESG1 基因定义为鼻咽癌(NPC)中的潜在肿瘤抑制基因。在这里,我们进一步使用蛋白质组学技术在 NPC 细胞中全面研究 NESG1 控制的蛋白质。蛋白质组学分析发现 26 种蛋白质受 NESG1 调控,而烯醇化酶 1(α)(ENO1)、热休克蛋白 90 kDa β (Grp94)、成员 1(HSP90B1)和组织蛋白酶 D(CTSD)蛋白通过 Western blot 显示差异表达。有趣的是,在 NPC 中过度表达的基因 a-烯醇化酶(ENO1)在 NPC 细胞中被确认为 NESG1 调节的蛋白质。过表达的 ENO1 不仅恢复了细胞增殖和细胞周期进程,而且拮抗了 NESG1 对细胞周期调节剂 p21 和 CCNA1 表达的调节,并诱导了 NESG1 过表达 NPC 细胞中 C-Myc、pRB 和 E2F1 的表达。实时 PCR 和免疫组织化学分析显示,在 NPC 组织中,NESG1 的表达与 ENO1 的表达呈负相关。我们的观察表明,ENO1 的下调在 NESG1 诱导的 NPC 癌细胞生长抑制中起着重要作用。

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