miR-944 acts as a prognostic marker and promotes the tumor progression in endometrial cancer.
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.
Department of Gynecology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, China.
Zhonghui
Z
He
Department of Gynecology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, China. Electronic address: xuhong_gxmu@163.com.
Hong
H
Xu
Department of Gynecology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, China.
Yugang
Y
Meng
Department of Gynecology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, China.
Yan
Y
Kuang
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018450:Disease Progression; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000473:pathology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D007150:Immunohistochemistry; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D011379:Prognosis
D014408:Biomarkers, Tumor; C556123:CADM2 protein, human; D015815:Cell Adhesion Molecules; C000603398:MIRN944 microRNA, human; D035683:MicroRNAs
Apoptosis; CADM2; Cell-cycle; EC; Proliferation; microRNA-944