MiR-429 Determines Poor Outcome and Inhibits Pancreatic Ductal Adenocarcinoma Growth by Targeting TBK1
MiR-429 Determines Poor Outcome and Inhibits Pancreatic Ductal Adenocarcinoma Growth by Targeting TBK1
复制标题
DOI：
10.1159/000373995
复制
发表时间：
2015-01-01
影响因子：
--
通讯作者：
Jin, Gang
中科院分区：
文献类型：
--
作者：
Song, Bin;Zheng, Kailian;Jin, Gang
背景：胰腺导管腺癌（Pancreatic ductal adenocarcinoma， PDAC）在癌症相关死亡原因中排名第四，其预后在过去几十年没有明显改善。mirna的失调或功能障碍有助于癌症的发展。先前的数据表明miR-429参与了PDAC的发病机制。然而，miR-429在PDAC中的作用仍然未知。方法：采用实时荧光定量PCR方法，检测78例患者样本组织以及PANC1和SW1990细胞系中MiR-429的水平。使用特异性的前mirna和抗mirna调节MiR-429的表达，并通过MTT分析检测细胞生长情况。对miR-429推测的靶基因进行了生物信息学预测，荧光素酶测定证实TBK1是直接靶基因。免疫组织化学分析PDAC组织中TBK1水平。结果：MiR-429在PDAC组织和细胞系中明显降低。PDAC组织中miR-429的低表达与PDAC患者的生存期缩短显著相关。过表达miR-429抑制PDAC细胞系的体外生长，反之亦然。TBK1被发现是miR-429的直接靶基因。PDAC组织中TBK1蛋白水平升高与PDAC患者的生存期缩短相关。TBK1过表达部分恢复细胞增殖。结论：PDAC中低水平的miR-429和高水平的TBK1促进了PDAC细胞的生长，这可能与PDAC患者的低生存率有关。MiR-429通过靶向TBK1在PDAC中发挥作用。巴塞尔S. Karger股份有限公司版权所有
Background: Pancreatic ductal adenocarcinoma (PDAC) ranks fourth on the list of cancer-related causes of death and its prognosis has not improved significantly over the past decades. Deregulation or dysfunction of miRNAs contribute to cancer development. Previous data indicates that miR-429 is involved in the pathogenesis of PDAC. However, the role of miR-429 in PDAC remained unknown. Methods: MiR-429 levels in sample tissues of 78 patients and in PANC1 and SW1990 cell lines were quantified by real-time PCR. MiR-429 expression was modulated using specific pre- and anti-miRNAs and cell growth was assayed by MTT analysis. Bioinformatics prediction of the miR-429 putative target genes was performed and luciferase assays confirmed TBK1 as a direct target gene. TBK1 levels in PDAC tissues were analyzed by immunohistochemistry. Results: MiR-429 was remarkably decreased in PDAC tissues and cell lines. Lower miR-429 expression in PDAC tissues significantly correlated with shorter survival of PDAC patients. Overexpression of miR-429 inhibited PDAC cell lines growth in vitro and vice versa. TBK1 was found to be the direct target gene of miR-429. Higher TBK1 protein level in PDAC tissues correlated with shorter survival of PDAC patients. Overexpression of TBK1 partly restored cell proliferation. Conclusions: Low level of miR-429 and high level of TBK1 in PDAC promoted PDAC cells growth which might be related to the low survival rate of PDAC patients. MiR-429 play its role in PDAC by targeting TBK1. Copyright (C) 2015 S. Karger AG, Basel