Low tristetraprolin expression promotes cell proliferation and predicts poor patients outcome in pancreatic cancer.
Low tristetraprolin expression promotes cell proliferation and predicts poor patients outcome in pancreatic cancer.
复制标题
三四脯氨酸低表达可促进细胞增殖并预测胰腺癌患者的不良预后。
DOI：
10.18632/oncotarget.7397
复制
发表时间：
2016-04-05
期刊：
影响因子：
--
通讯作者：
Cai QP
中科院分区：
文献类型：
--
作者：
Wei ZR;Liang C;Feng D;Cheng YJ;Wang WM;Yang DJ;Wang YX;Cai QP
Tristetraprolin（也称为TTP，TIS 11，ZFP 36和Nup 475）是一种在几种肿瘤类型中下调的肿瘤抑制因子。在目前的研究中，我们发现，TTP的表达显着降低胰腺癌样本相比，匹配的正常组织。低TTP水平与年龄（P=0.037）、肿瘤大小（P=0.008）、肿瘤分化程度（P=0.004）、术后T分期（P<0.001）、术后N分期（P=0.008）和TNM分期（P<0.001）有关。此外，低TTP表达预示着生存率降低和患者预后不良。我们还发现，TTP损害胰腺癌细胞增殖在体内和体外。荧光激活细胞分选（FACS）分析表明，TTP过表达既增加胰腺癌细胞的凋亡，又降低其增殖。RNA测序分析表明，TTP过表达下调几种肿瘤相关因子，包括Pim-1和IL-6。我们的研究结果表明，TTP可以作为胰腺癌的一个潜在的预后指标。
Tristetraprolin (also known as TTP, TIS11, ZFP36, and Nup475) is a well-characterized tumor suppressor that is down-regulated in several tumor types. In the current study, we found that TTP expression was markedly reduced in pancreatic cancer samples as compared to matched normal tissues. Low TTP level was associated with age (P=0.037), tumor size (P=0.008), tumor differentiation (P=0.004), postoperative T stage (pT stage, P<0.001), postoperative N stage (pN stage, P=0.008) and TNM stage (P<0.001). Moreover, low TTP expression predicted reduced survival rates and poor patient outcome. We also found that TTP impairs pancreatic cancer cell proliferation both in vivo and in vitro. Fluorescence Activated Cell Sorting (FACS) assay showed that TTP over-expression both increases apoptosis and decreases proliferation in pancreatic cancer cells. RNA-sequencing analysis showed that TTP over-expression downregulates several tumor-related factors, including Pim-1 and IL-6. Our findings indicate that TTP could serve as a potential prognostic indicator in pancreatic cancer.