miR-942 promotes cancer stem cell-like traits in esophageal squamous cell carcinoma through activation of Wnt/β-catenin signalling pathway
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Chunlei Ge1,*, Shikai Wu2,*, Weiwei Wang3,*, Zhimin Liu1, Jianhua Zhang1, Zhenyu Wang4, Ruilei Li1, Zhiwei Zhang1, Zhen Li1, Suwei Dong1, Ying Wang1, Yuanbo Xue1, Jinyan Yang1, Qinghua Tan1, Ziping Wang5 and Xin Song1
1 Department of Cancer Biotherapy Center, The Third Affiliated Hospital of Kunming Medical University (Tumor Hospital of Yunnan Province), Kunming, Yunnan, People’s Republic of China
2 Department of Radiation Oncology, Affiliated Hospital of Academy of Military Medical Sciences, Beijing, People’s Republic of China
3 Department of Thoracic Surgery, The Third Affiliated Hospital of Kunming Medical University (Tumor Hospital of Yunnan Province), Kunming, Yunnan, People’s Republic of China
4 Department of Biomedical Engineering Research Center, Kunming Medical University, Kunming, Yunnan, People’s Republic of China
5 Department of Medical Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences (CAMS), Beijing, People’s Republic of China
* These authors have contributed equally to this work
Xin Song, email:
Ziping Wang, email:
Keywords: miR-942, cancer stem cells, Wnt/β-catenin signalling pathway, esophageal squamous cell carcinoma
Received: December 20, 2014 Accepted: March 02, 2015 Published: March 30, 2015
The Wnt/β-catenin signalling pathway is known to play a vital role in the maintenance of cancer stem cells (CSCs), which are reported to be the origine of malignant cancers, and result in poor prognosis of multiple kinds of cancer. Therefore, it is of great importance to illuminate the mechanism by which the Wnt/β-catenin pathway regulates the cancer stem cell-like traits in cancers. Here, we report that miR-942 is significantly upregulated in esophageal squamous cell carcinoma (ESCC), and miR-942 levels are associated with poor prognosis in ESCC patients. Overexpression of miR-942 promotes, whereas inhibition of miR-942 decreases, the tumor sphere formation, the CD90+ subpopulation cells and the expression of pluripotency associated markers. Moreover, in vivo assay shows that miR-942 overexpressing cells form larger tumors and display higher tumourigenesis. Furthermore, we demonstrate that miR-942 upregulates the Wnt/β-catenin signaling activity via directly targeting sFRP4, GSK3β and TLE1, which are multiple level negative regulators of the Wnt/β-catenin signaling cascade. In addition, our results indicate that c-myc directly binds to the miR-942 promoter and promotes its expression. Taken together, our findings establish an oncogenic role of miR-942 in ESCC and indicate that miR-942 might be an effective therapeutic target for ESCC.
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