MiR-1207 overexpression promotes cancer stem cell-like traits in ovarian cancer by activating the Wnt/β-catenin signaling pathway

// Geyan Wu 1, 2, 3, * , Aibin Liu 1, * , Jinrong Zhu 1 , Fangyong Lei 2 , Shu Wu 2 , Xin Zhang 2 , Liping Ye 2 , Lixue Cao 1 , Shanyang He 1 1 Department of Obstetrics and Gynecology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510700, PR China 2 State Key Laboratory of Oncology in Southern China, Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou 510060, PR China 3 Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, PR China * These authors have contributed equally to this work Correspondence to: Shanyang He, e-mail: heshanyang1976@163.com Keywords: ovarian cancer, Wnt/β-catenin signaling, cancer stem cells, tumorigenicity Received: March 29, 2015 Accepted: August 07, 2015 Published: August 17, 2015 ABSTRACT Wnt/β-catenin signaling pathway is strictly controlled by multiple negative regulators. However, how tumor cells override the negative regulatory effects to maintain constitutive activation of Wnt/β-catenin signaling, which is commonly observed in various cancers, remains puzzling. In current study, we reported that overexpression of miR-1207 in ovarian cancer activated Wnt/β-catenin signaling by directly targeting and suppressing secreted Frizzled-related protein 1 (SFRP1), AXIN2 and inhibitor of β-catenin and TCF-4 (ICAT), which are vital negative regulators of the Wnt/β-catenin pathway. We found that the expression of miR-1207 was ubiquitously upregulated in both ovarian cancer tissues and cells, which inversely correlated with patient overall survival. Furthermore, overexpression of miR-1207 enhanced, while silencing miR-1207 reduced, stem cell-like traits of ovarian cancer cells in vitro and in vivo , including tumor sphere formation capability and proportion of SP+ and CD133+ cells. Importantly, upregulating miR-1207 promoted, while silencing miR-1207 inhibited, the tumorigenicity of ovarian cancer cells. Hence, our results suggest that miR-1207 plays a vital role in promoting the cancer stem cell-like phenotype in ovarian cancer and might represent a potential target for anti-ovarian cancer therapy.