Up-regulation of microRNA-145 promotes differentiation by repressing OCT4 in human endometrial adenocarcinoma cells
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BACKGROUND: MicroRNA-145 (miR-145) has been reported to be a tumor-suppressing agent in several studies. It can repress pluripotency and control human embryonic stem cell differentiation by regulating the core pluripotency factor OCT4. However, it is not known whether miR-145 can play a role in inducing tumor cell differentiation and repressing growth of tumors. METHODS: Ishikawa cells, the established human endometrial cancer cells, were treated with miR-145 mimics, inhibitor, or small interfering RNA OCT4. miR-145 levels were assayed using TaqMan microRNA assays, and the messenger RNA levels of OCT4 and the differentiation marker glycodelin were measured using real-time polymerase chain reaction. The protein levels of OCT4 and glycodelin were characterized via flow cytometry, western blotting, and immunohistochemistry. In vivo activity was measured in a xenograft mouse model. RESULTS: Up-regulating miR-145 reduced the expression of OCT4 and induced the differentiation of Ishikawa cells to closely resemble normal endometrial epithelium both in vitro and in vivo. miR-145 successfully inhibited tumor growth. We also found that in patients with endometrial carcinoma, miR-145 and OCT4 were expressed in tissues, and there was a relationship between miR-145, OCT4, and the degree of tumor cell differentiation. CONCLUSIONS: Our results strongly suggested that miR-145 is a tumor cell differentiation-inducing agent in endometrial carcinoma, and that miR-145 or OCT4 may be useful markers for grading endometrial carcinoma.
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