YB-1 expression promotes pancreatic cancer metastasis that is inhibited by microRNA-216a
YB-1 expression promotes pancreatic cancer metastasis that is inhibited by microRNA-216a
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YB-1 表达促进胰腺癌转移，但 microRNA-216a 抑制该转移
DOI：
10.1016/j.yexcr.2017.07.039
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发表时间：
2017-10-15
影响因子：
3.7
通讯作者：
Wang, Zhiwei
中科院分区：
文献类型：
--
作者：
Lu, Jingjing;Li, Xiaohong;Wang, Zhiwei
胰腺癌是最具侵袭性的癌症之一。绝大多数患者由于早期浸润性生长和转移性扩散而被诊断为晚期、不可切除的疾病。本研究的目的是检测YB-1在胰腺癌中的表达，并确定其对细胞侵袭的影响。YB-1在胰腺癌细胞系和患者组织样品中过表达。在患者组织中，高YB-1水平与神经周围浸润相关。YB-1基因的沉默显著降低了细胞的侵袭能力，同时降低了MMPs的表达。此外，我们发现miR-216 a通过直接结合YB-1 3 '非翻译区抑制YB-1的表达。miR-216 a和YB-1表达水平在胰腺癌细胞系中呈负相关。此外，miR-216 a的异位表达在体外抑制细胞侵袭。总之，我们的研究结果表明，YB-1可能在介导转移行为中起重要作用，并且miR-216 a对YB-1的抑制可能具有抑制胰腺癌肿瘤转移的有希望的治疗潜力。
Pancreatic cancer is one of the most aggressive cancers. The vast majority of patients are diagnosed with advanced, unresectable disease because of early invasive growth and metastatic spread. The aim of this study was to examine YB-1 expression in pancreatic cancer and determine its effects on cell invasion. YB-1 is overexpressed in pancreatic cancer cell lines and patient tissue samples. In patient tissues, high YB-1 levels correlated with perineural invasion. Silencing of YB-1 significantly reduced cell invasion with decreased expression of MMPs in vitro. Furthermore, we found that the expression of YB-1 was suppressed by miR-216a via direct binding to the YB-1 3'-untranslated region. MiR-216a and YB-1 expression levels were inversely correlated in pancreatic cancer cell lines. In addition, ectopic expression of miR-216a inhibited cell invasion in vitro. Taken together, our findings suggest that YB-1 may play an important role in mediating metastatic behaviour and that repression of YB-1 by miR-216a could have a promising therapeutic potential to inhibit tumor metastasis in pancreatic cancer.