Linc-RoR promotes proliferation, migration, and invasion via the Hippo/YAP pathway in pancreatic cancer cells
Linc-RoR promotes proliferation, migration, and invasion via the Hippo/YAP pathway in pancreatic cancer cells
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Linc-RoR 通过 Hippo/YAP 通路促进胰腺癌细胞的增殖、迁移和侵袭
DOI：
10.1002/jcb.29308
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发表时间：
2019-08-26
影响因子：
4
通讯作者：
Xu, Min
中科院分区：
文献类型：
--
作者：
Chen, Wei;Wang, Huizhi;Xu, Min
大基因间非编码RNA重编程调节因子（Linc-RoR）是最早发现的一种通过重编程分化细胞来增加诱导多能干细胞出现的调节因子，在多种恶性肿瘤中异常表达。然而，Linc-RoR在胰腺癌进展中的功能需要进一步阐明。本研究的数据表明，Linc-RoR敲低抑制细胞增殖能力和集落形成，而Linc-RoR过表达促进这些行为。Linc-RoR过表达可促进胰腺癌细胞间充质标志物的表达，抑制上皮标志物的表达，增强胰腺癌细胞的迁移和侵袭能力; Linc-RoR敲低可抑制胰腺癌细胞间充质标志物的表达，促进上皮标志物的表达，减弱胰腺癌细胞的迁移和侵袭能力。进一步的研究表明，Linc-RoR敲低导致雅普磷酸化显着下降，总雅普磷酸化上升，而Linc-RoR过表达则产生相反的结果。具体而言，Linc-RoR促进细胞质中的雅普进入细胞核。综上所述，我们证实Linc-RoR通过激活Hippo/雅普通路促进胰腺癌细胞的增殖、迁移和侵袭。雅普可能是Linc-RoR的潜在靶点，并介导胰腺癌的上皮-间质转化（EMT），因此Linc-RoR可能是一个非常有意义的胰腺癌生物标志物。
Large intergenic noncoding RNA regulator of reprogramming (Linc-RoR) was first identified as a regulator to increase the emergence of induced pluripotent stem cells through reprogramming differentiated cells and is abnormal expression in a variety of malignant tumors. However, the function of Linc-RoR in pancreatic cancer progression needs further clarification. The data from this study demonstrated that Linc-RoR knockdown suppressed cell proliferative capacity and colony formation, while Linc-RoR overexpression promoted these behaviors. In particular, Linc-RoR overexpression promoted the level of mesenchymal markers, inhibited the expression of epithelial markers, as well as enhanced pancreatic cancer cells migration and invasion, whereas Linc-RoR knockdown inhibited the expression of mesenchymal markers, promoted the expression of epithelial markers, as well as weakened pancreatic cancer cells migration and invasion. Further study revealed that Linc-RoR knockdown brought about a significant fall in YAP phosphorylation and a rise in total YAP, while Linc-RoR overexpression produced the opposite results. Specifically, Linc-RoR promoted YAP in the cytoplasm into the nucleus. Taken together, we conjectured that Linc-RoR promoted proliferation, migration, and invasion of pancreatic cancer cells by activating the Hippo/YAP pathway. YAP might be an underlying target of Linc-RoR and mediate epithelial-mesenchymal transition (EMT) in pancreatic cancer (PC); thus, Linc-RoR might be a very meaningful biomarker for PC.