YTH domain family 2 orchestrates epithelial-mesenchymal transition/proliferation dichotomy in pancreatic cancer cells
YTH domain family 2 orchestrates epithelial-mesenchymal transition/proliferation dichotomy in pancreatic cancer cells
复制标题
YTH 结构域家族 2 协调胰腺癌细胞中的上皮-间质转化/增殖二分法
DOI：
10.1080/15384101.2017.1380125
复制
发表时间：
2017-01-01
期刊：
影响因子：
4.3
通讯作者：
Xu, Min
中科院分区：
文献类型：
--
作者：
Chen, Jixiang;Sun, Yaocheng;Xu, Min
近年来的研究表明，YTH结构域家族2（YTHDF 2）优先与含有m6 A的mRNA结合，调节结合mRNA的定位和稳定性。然而，YTHDF 2在胰腺癌中的作用仍有待阐明。在此，我们发现YTHDF 2在胰腺癌组织中的表达在mRNA和蛋白水平上均高于正常组织，并且在临床晚期胰腺癌患者中更高，表明YTHDF 2对胰腺癌的诊断和预后具有潜在的临床意义。此外，我们发现YTHDF 2协调两个细胞过程：促进胰腺癌细胞的增殖并抑制其迁移和侵袭，这一现象称为“迁移-增殖二分法”，以及胰腺癌细胞的上皮-间质转化（EMT）。此外，YTHDF 2基因敲低可显著增加总雅普表达，但抑制TGF-β/Smad信号，表明YTHDF 2可能通过雅普信号调节EMT。总之，所有这些发现表明YTHDF 2可能是胰腺癌发展的新的预测生物标志物，但需要认真考虑将YTHDF 2作为胰腺癌的靶点。
ABSTRACT Recent studies show that YTH domain family 2 (YTHDF2) preferentially binds to m6A-containing mRNA regulates localization and stability of the bound mRNA. However, the role of YTHDF2 in pancreatic cancers remains to be elucidated. Here, we find that YTHDF2 expression is up-regulated in pancreatic cancer tissues compared with normal tissues at both mRNA and protein levels, and is higher in clinical patients with later stages of pancreatic cancer, indicating that YTHDF2 possesses potential clinical significance for diagnosis and prognosis of pancreatic cancers. Furthermore, we find that YTHDF2 orchestrates two cellular processes: promotes proliferation and inhibits migration and invasion in pancreatic cancer cells, a phenomenon called “migration-proliferation dichotomy”, as well as epithelial-mesenchymal transition (EMT) in pancreatic cancer cells. Furthermore, YTHDF2 knockdown significantly increases the total YAP expression, but inhibits TGF-β/Smad signaling, indicating that YTHDF2 regulates EMT probably via YAP signaling. In summary, all these findings suggest that YTHDF2 may be a new predictive biomarker of development of pancreatic cancer, but a serious consideration is needed to treat YTHDF2 as a target for pancreatic cancer.