microRNA-944 (miR-944) has been reported to be deregulation and play either tumor suppressive or oncogenic function in human malignancies. Previous studies have reported that miR-944 is overexpressed in gynecological malignancies including cervical cancer and breast cancer. While, the clinical significance of miR-944 and its function in human endometrial carcinoma (EC) keep unknown. The levels of miR-944 were analyzed in 68 EC tissues and 20 normal endometrial tissues. Results showed that miR-944 was significantly overexpressed in EC tissues compared to normal endometrial tissues. In addition, increased levels of miR-944 also observed in EC cell lines. Clinicopathological analysis verified that miR-944 expression was associated with international federation of gynecology and obstetrics (FIGO) stages and pathology classification of EC. Moreover, Kaplan-Meier analysis found that miR-944 highly expressing EC patients showed a notable shorter survival. Further experiments revealed that miR-944 knockdown significantly inhibited growth and cell cycle progression while facilitated apoptosis in Ishikawa cells. In turn, miR-944 overexpression prominently promoted proliferation and cell cycle progression, and suppressed apoptosis in KLE cells. In vivo experiments further confirmed that miR-944 silencing notably restrained the tumor growth of EC in nude mice. Mechanically, cell adhesion molecule 2 (CADM2) was recognized as a direct downstream target of miR-944 in EC cells. An inverse correlation between miR-944 and CADM2 expression was observed in EC tissues. Interestingly, CADM2 overexpression showed similar effects to miR-944 knockdown in Ishikawa cells with decreased growth, cell cycle arrest at G1 phase and increased apoptosis. Taken together, this work support the first evidence that miR-944 can be potentially used as a promising biomarker and novel therapeutic target for human EC.
Keywords: Apoptosis; CADM2; Cell-cycle; EC; Proliferation; microRNA-944.
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