The Wnt/beta-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/beta-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/beta-catenin signaling activity via directly targeting sFRP4, GSK3 beta and TLE1, which are multiple level negative regulators of the Wnt/beta-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.
[1]Kunming Med Univ, Affiliated Hosp 3, Tumor Hosp Yunnan Prov, Dept Canc Biotherapy Ctr, Kunming, Yunnan, Peoples R China.
[2]Acad Mil Med Sci, Affiliated Hosp, Dept Radiat Oncol, Beijing, Peoples R China.
[3]Kunming Med Univ, Affiliated Hosp 3, Tumor Hosp Yunnan Prov, Dept Thorac Surg, Kunming, Yunnan, Peoples R China.
[4]Kunming Med Univ, Dept Biomed Engn, Res Ctr, Kunming, Yunnan, Peoples R China.
[5]Chinese Acad Med Sci, Canc Inst & Hosp, Dept Med Oncol, Beijing 100730, Peoples R China.
(8.0+极速模式)