期刊
ONCOTARGET
卷 6, 期 30, 页码 28882-28894出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.4921
关键词
ovarian cancer; Wnt/beta-catenin signaling; cancer stem cells; tumorigenicity
资金
- Science and Technology Planning Project of Guangdong Province, China [S2013010015599, 2011B031800100]
- National Natural Scientific Foundation of China [81272196, 81325013, 81272198, U1201121]
Wnt/beta-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/beta-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/beta-catenin signaling by directly targeting and suppressing secreted Frizzled-related protein 1 (SFRP1), AXIN2 and inhibitor of beta-catenin and TCF-4 (ICAT), which are vital negative regulators of the Wnt/beta-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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