MicroRNA-145 Promotes Human Endometrial Adenocarcinoma Cells Differentiation by Repressing OCT4

Abstract

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. the established human endometrial cancer cells, Ishikawa 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 realtime 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. As a result, 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. In 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.