Lu Jingjing, Li Xiaohong, Wang Fei, Guo Yibing, Huang Yan, Zhu Hui, Wang Yao, Lu Yuhua, Wang Zhiwei
Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province 226001, PR China.
Department of General Surgery, The First People's Hospital of Nantong, Jiangsu Province 226001, PR China.
Exp Cell Res. 2017 Oct 15;359(2):319-326. doi: 10.1016/j.yexcr.2017.07.039. Epub 2017 Aug 3.
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.
胰腺癌是侵袭性最强的癌症之一。由于早期侵袭性生长和转移扩散,绝大多数患者被诊断为晚期、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本中过表达。在患者组织中,高YB-1水平与神经周围侵犯相关。在体外,沉默YB-1可显著降低细胞侵袭,同时基质金属蛋白酶的表达也降低。此外,我们发现miR-216a通过直接结合YB-1的3'-非翻译区来抑制YB-1的表达。在胰腺癌细胞系中,miR-216a和YB-1的表达水平呈负相关。此外,miR-216a的异位表达在体外抑制细胞侵袭。综上所述,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-216a对YB-1的抑制可能具有抑制胰腺癌肿瘤转移的潜在治疗前景。