MiR-744 increases tumorigenicity of pancreatic cancer by activating Wnt/β-catenin pathway
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Wei Zhou1, Yongfeng Li1, Shanmiao Gou1, Jiongxin Xiong1, Heshui Wu1, Chunyou Wang1, Haijiao Yan2, Tao Liu1,3
1Pancreatic Disease Institute, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, P.R. China
2Department of Oncology, the Third Affiliated Hospital of Soochow University, Changzhou, 213003, P.R. China
3Department of Digestive Surgical Oncology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, P.R. China
Tao Liu, e-mail: Uniontao@hust.edu.cn
Haijiao Yan, e-mail: firstname.lastname@example.org
Keywords: miR-744, pancreatic cancer, Wnt/β-catenin signaling, cancer stem cells, tumorigenicity
Received: April 26, 2015 Accepted: October 02, 2015 Published: October 15, 2015
The Wnt/β-catenin signaling pathway, commonly hyperactivated in pancreatic cancer, has been reported to play an important role in the maintenance of stemness of cancer stem cells (CSCs), which is closely related to the progression of pancreatic cancer. Therefore, exploring the regulatory mechanism in Wnt/β-catenin signaling may provide valuable clinical targets for cancer therapy. In the current study, we demonstrated that upregulation of miR-744 in pancreatic cancer promoted Wnt/β-catenin signaling by directly targeting secreted frizzled-related protein 1 (SFRP1), glycogen synthase kinase 3β (GSK3β), and transducin-like enhancer of split 3 (TLE3), important negative modulators of Wnt/β-catenin signaling. Expression of miR-744 was markedly upregulated in pancreatic cancer and positively correlated with poor patient survival. Furthermore, we found that overexpressing miR-744 enhanced, while inhibiting miR-744 reduced, the stem cell-like phenotype of pancreatic cancer cells in vitro. Importantly, in vivo model of human-derived pancreatic xenografts showed that miR-744 upregulation enhanced the tumorigenicity of pancreatic cancer cells. These findings suggest that miR-744 plays a vital role in promoting the stem cell-like phenotype of pancreatic cancer cells, and may represent a novel prognostic biomarker and therapeutic target.
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