推荐产品
公司新闻/正文
华中科技大学发现肝癌预后新标志物
人阅读 发布时间：2014-07-08 11:30
近期，来自华中科技大学同济医学院的研究者在国际著名肝脏疾病杂志Hepatology发布了其最新研究成果，该研究中，研究者发现，转录中介因子TIF1γ在肝癌细胞中会出现下调，这种下调会促进癌细胞转移，从而产生不良预后效果。
肝癌是一类致死率非常高的恶性肿瘤，由于手术切除后常常出现癌症复发和转移，故预后效果常常很差，关于关于癌细胞复发及转移的分子机制仍有待进一步深入研究。在此项研究中，研究人员证实肝癌细胞中TIF1γ多呈低表达，且低表达的肝癌患者总生存时间缩短、复发率较高；进一步机制研究发现，在肝癌发生的不同阶段，TIF1γ会通过调控TGF-β/Smad信号通路，发挥不同功能：在肝癌早期，它会促进癌细胞生长，却又会抑制癌细胞侵袭和转移；而在肝癌晚期，虽然它不再促进癌细胞生长，却依然具有抑制癌细胞侵袭和转移的能力。研究者发现，是肝癌细胞中TIF1γ基因启动子上的CpG岛超甲基化作用，导致了TIF1γ下调，从而减弱了对肝癌细胞侵袭与转移的抑制。基于TIF1γ的这些特性，研究者认为，它可以成为肝癌预后的一个标志物，用于预测肝癌转移及预后效果。
锐博生物推荐原文摘要
Reduced Expression of TIF1γ Promotes Metastasis and Indicates Poor Prognosis of Hepatocellular Carcinoma
Transcriptional intermediary factor 1 γ (TIF1γ) may play either potential tumor suppressor or promoter role in cancer. Herein we reported a critical role of TIF1γ in the progression of hepatocellular carcinoma (HCC). Reduced expression of TIF1γ was detected in HCC, especially in advance HCC tissues compared with adjacent noncancerous tissues. HCC patients with low-TIF1γ expression had shorter overall survival times and higher recurrence rates than those with high-TIF1γ expression. Reduced TIF1γ expression was an independent and significant risk factor for recurrence and survival after curative resection. In HCC cells, TIF1γ played a dual role: it promoted tumor growth in early stage HCC but not in advanced stage HCC, whereas it inhibited invasion and metastasis in both early stage and advanced stage HCC. Mechanistically, we confirmed that TIF1γ inhibited transforming growth factor-β/drosophila mothers against decapentaplegic protein (TGF-β/Smad) signaling through monoubiquitination of Smad4 and suppressed the formation of Smad2/3/4 complex in HCC cells. TGF-β inducing cytostasis and metastasis were both inhibited by TIF1γ in HCC. We further proved that TIF1γ suppressed cyotstasis related TGF-β/Smad downstream c-myc downregulation, as well as p21/cip1 and p15/ink4b upregulation in early stage HCC. Meanwhile, TGF-β inducible epithelial-mesenchymal transition and TGF-β/Smad downstream metastatic cascades, including PTEN downregulation, CXCR4 and MMP1 induction and EGFR and Akt signaling transactivation, were inhibited by TIF1γ. In addition, we found that the downregulation of TIF1γ in HCC was caused by hypermethylation of CpG islands in TIF1γ promoter, and demonstrated that the combination of TIF1γ and p-Smad2 was a more powerful predictor of poor prognosis. Conclusion: TIF1γ regulates tumor growth and metastasis through inhibition of TGF-β/Smad signaling and may serve as a novel prognostic biomarker in HCC.
肝癌是一类致死率非常高的恶性肿瘤，由于手术切除后常常出现癌症复发和转移，故预后效果常常很差，关于关于癌细胞复发及转移的分子机制仍有待进一步深入研究。在此项研究中，研究人员证实肝癌细胞中TIF1γ多呈低表达，且低表达的肝癌患者总生存时间缩短、复发率较高；进一步机制研究发现，在肝癌发生的不同阶段，TIF1γ会通过调控TGF-β/Smad信号通路，发挥不同功能：在肝癌早期，它会促进癌细胞生长，却又会抑制癌细胞侵袭和转移；而在肝癌晚期，虽然它不再促进癌细胞生长，却依然具有抑制癌细胞侵袭和转移的能力。研究者发现，是肝癌细胞中TIF1γ基因启动子上的CpG岛超甲基化作用，导致了TIF1γ下调，从而减弱了对肝癌细胞侵袭与转移的抑制。基于TIF1γ的这些特性，研究者认为，它可以成为肝癌预后的一个标志物，用于预测肝癌转移及预后效果。
图1 TIF1γ抑制肝癌细胞侵袭与转移通路示意图
图2 用EdU检测Huh7细胞敲除TIF1γ后增殖状况
在该研究中，研究者使用锐博生物所开发的EdU类产品，检测敲除TIF1γ后细胞增殖状况，效果明显，显示出该产品优秀品质。同时，锐博生物还为研究者建立了以EdU为核心的细胞组织分析平台，提供包括细胞增殖检测、细胞凋亡检测、细胞标记示踪、DNA损伤修复检测、线粒体活性检测、病毒增殖活性检测及RNA转录活性检测等全面的细胞服务，为您带来最清晰最准确的细胞水平研究结果，是您最值得信赖的研究伙伴！
锐博生物推荐原文摘要
Reduced Expression of TIF1γ Promotes Metastasis and Indicates Poor Prognosis of Hepatocellular Carcinoma
Transcriptional intermediary factor 1 γ (TIF1γ) may play either potential tumor suppressor or promoter role in cancer. Herein we reported a critical role of TIF1γ in the progression of hepatocellular carcinoma (HCC). Reduced expression of TIF1γ was detected in HCC, especially in advance HCC tissues compared with adjacent noncancerous tissues. HCC patients with low-TIF1γ expression had shorter overall survival times and higher recurrence rates than those with high-TIF1γ expression. Reduced TIF1γ expression was an independent and significant risk factor for recurrence and survival after curative resection. In HCC cells, TIF1γ played a dual role: it promoted tumor growth in early stage HCC but not in advanced stage HCC, whereas it inhibited invasion and metastasis in both early stage and advanced stage HCC. Mechanistically, we confirmed that TIF1γ inhibited transforming growth factor-β/drosophila mothers against decapentaplegic protein (TGF-β/Smad) signaling through monoubiquitination of Smad4 and suppressed the formation of Smad2/3/4 complex in HCC cells. TGF-β inducing cytostasis and metastasis were both inhibited by TIF1γ in HCC. We further proved that TIF1γ suppressed cyotstasis related TGF-β/Smad downstream c-myc downregulation, as well as p21/cip1 and p15/ink4b upregulation in early stage HCC. Meanwhile, TGF-β inducible epithelial-mesenchymal transition and TGF-β/Smad downstream metastatic cascades, including PTEN downregulation, CXCR4 and MMP1 induction and EGFR and Akt signaling transactivation, were inhibited by TIF1γ. In addition, we found that the downregulation of TIF1γ in HCC was caused by hypermethylation of CpG islands in TIF1γ promoter, and demonstrated that the combination of TIF1γ and p-Smad2 was a more powerful predictor of poor prognosis. Conclusion: TIF1γ regulates tumor growth and metastasis through inhibition of TGF-β/Smad signaling and may serve as a novel prognostic biomarker in HCC.
询价列表
暂时没有已询价产品
快捷询价 发送名片
当你希望让更多商家联系你时，可以勾选后发送询价，平台会将你的询价消息推荐给更多商家。