%0 Journal Article %1 xie2018let7c %A Xie, Y %A Zhang, H %A Guo, X J %A Feng, Y C %A He, R Z %A Li, X %A Yu, S %A Zhao, Y %A Shen, M %A Zhu, F %A Wang, X %A Wang, M %A Balakrishnan, A %A Ott, M %A Peng, F %A Qin, R Y %D 2018 %E Dis, Cell Death %J Cell Death & Disease %K Ott %N 2 %P 249 %T Let-7c inhibits cholangiocarcinoma growth but promotes tumor cell invasion and growth at extrahepatic sites %V 9 %X Cholangiocarcinoma (CCA) is a cancer type with high postoperative relapse rates and poor long-term survival largely due to tumor invasion, distant metastasis, and multidrug resistance. Deregulated microRNAs (miRNAs) are implicated in several cancer types including CCA. The specific roles of the miRNA let-7c in cholangiocarcinoma are not known and need to be further elucidated. In our translational study we show that microRNA let-7c expression was significantly downregulated in human cholangiocarcinoma tissues when compared to adjacent tissues of the same patient. Let-7c inhibited the tumorigenic properties of cholangiocarcinoma cells including their self-renewal capacity and sphere formation in vitro and subcutaneous cancer cell growth in vivo. Ectopic let-7c overexpression suppressed migration and invasion capacities of cholangiocarcinoma cell lines in vitro, however, promoted distant invasiveness in vivo. Furthermore, we found that let-7c regulated the aforementioned malignant biological properties, at least in part, through regulation of EZH2 protein expression and through the DVL3/β-catenin axis. The miRNA let-7c thus plays an important dual role in regulating tumorigenic and metastatic abilities of human cholangiocarcinoma through mechanisms involving EZH2 protein and the DVL3/β-catenin axis.

@article{xie2018let7c, abstract = {Cholangiocarcinoma (CCA) is a cancer type with high postoperative relapse rates and poor long-term survival largely due to tumor invasion, distant metastasis, and multidrug resistance. Deregulated microRNAs (miRNAs) are implicated in several cancer types including CCA. The specific roles of the miRNA let-7c in cholangiocarcinoma are not known and need to be further elucidated. In our translational study we show that microRNA let-7c expression was significantly downregulated in human cholangiocarcinoma tissues when compared to adjacent tissues of the same patient. Let-7c inhibited the tumorigenic properties of cholangiocarcinoma cells including their self-renewal capacity and sphere formation in vitro and subcutaneous cancer cell growth in vivo. Ectopic let-7c overexpression suppressed migration and invasion capacities of cholangiocarcinoma cell lines in vitro, however, promoted distant invasiveness in vivo. Furthermore, we found that let-7c regulated the aforementioned malignant biological properties, at least in part, through regulation of EZH2 protein expression and through the DVL3/β-catenin axis. The miRNA let-7c thus plays an important dual role in regulating tumorigenic and metastatic abilities of human cholangiocarcinoma through mechanisms involving EZH2 protein and the DVL3/β-catenin axis.}, added-at = {2018-03-01T13:45:45.000+0100}, author = {Xie, Y and Zhang, H and Guo, X J and Feng, Y C and He, R Z and Li, X and Yu, S and Zhao, Y and Shen, M and Zhu, F and Wang, X and Wang, M and Balakrishnan, A and Ott, M and Peng, F and Qin, R Y}, biburl = {https://www.bibsonomy.org/bibtex/21e519e8751b6fb36b2b57db4dedc66b4/ott}, editor = {Dis, Cell Death}, interhash = {4945afa606c580baad75294ffc1dcc87}, intrahash = {1e519e8751b6fb36b2b57db4dedc66b4}, journal = {Cell Death & Disease}, keywords = {Ott}, number = 2, pages = 249, pubmedurl = {https://www.ncbi.nlm.nih.gov/pubmed/29445149}, timestamp = {2018-03-01T13:45:45.000+0100}, title = {Let-7c inhibits cholangiocarcinoma growth but promotes tumor cell invasion and growth at extrahepatic sites}, volume = 9, year = 2018 }