MiR-1207 overexpression promotes cancer stem cell–like traits in ovarian cancer by activating the Wnt/β-catenin signaling pathway
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Geyan Wu1,2,3,*, Aibin Liu1,*, Jinrong Zhu1, Fangyong Lei2, Shu Wu2, Xin Zhang2, Liping Ye2, Lixue Cao1, Shanyang He1
1Department of Obstetrics and Gynecology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510700, PR China
2State Key Laboratory of Oncology in Southern China, Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou 510060, PR China
3Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, PR China
*These authors have contributed equally to this work
Shanyang He, e-mail: firstname.lastname@example.org
Keywords: ovarian cancer, Wnt/β-catenin signaling, cancer stem cells, tumorigenicity
Received: March 29, 2015 Accepted: August 07, 2015 Published: August 17, 2015
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.
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