MiR-125a suppresses tumor growth, invasion and metastasis in cervical cancer by targeting STAT3

被引:136
作者
Fan, Zhongyi [1 ]
Cui, Hanzhi [2 ]
Xu, Xiaojie [3 ]
Lin, Zhi [1 ]
Zhang, Xuelin [1 ]
Kang, Lei [4 ]
Han, Baiyu [5 ]
Meng, Jing [1 ]
Yan, Zhifeng [1 ]
Yan, Xiang [1 ]
Jiao, Shunchang [1 ]
机构
[1] Peoples Liberat Army Gen Hosp, Dept Oncol, Beijing, Peoples R China
[2] 309th Hosp PLA, Dept Oncol, Beijing, Peoples R China
[3] Beijing Inst Biotechnol, Dept Med Mol Biol, Beijing, Peoples R China
[4] Peking Univ, Hosp 1, Dept Nucl Med, Beijing 100871, Peoples R China
[5] 264th Hosp PLA, Dept Endocrinol & Metablism, Taiyuan, Shanxi, Peoples R China
关键词
miR-125a; cervical cancer; cell growth; metastasis; STAT3; EPITHELIAL-MESENCHYMAL TRANSITION; LYMPH-NODE METASTASIS; HUMAN-PAPILLOMAVIRUS; GERMLINE MUTATION; SIGNAL TRANSDUCER; EXPRESSION; OVEREXPRESSION; INHIBITION; PROGNOSIS; APOPTOSIS;
D O I
10.18632/oncotarget.4457
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
MiR-125a has been characterized as a tumor suppressor in several cancers. However, the role of miR-125a in cervical cancer is unknown. In this study, we found the expression of miR-125a was downregulated in cervical cancer patients, and negatively correlated with the tumor size, FIGO stage, and preoperative metastasis. Kaplan-Meier analysis showed that miR-125a expression predicted favorable outcome for cervical cancer patients. Dual luciferase assays identified the STAT3 gene as a novel direct target of miR-125a. Functional studies showed that miR-125a overexpression significantly suppressed the growth, invasion and epithelial-mesenchymal transition (EMT) of cervical cancer cells both in vitro and in vivo via decreasing STAT3 expression. Moreover, miR-125a conferred to G2/M cell cycle arrest, accompanied by inhibition of several G2/M checkpoint proteins. Mechanistically, inactivation of miR-125a during cervical carcinogenesis was caused by HPV suppression of p53 expression. Clinically, STAT3, the expression of which, predicted poorer outcome, was inversely correlated with miR-125a in cervical cancer. These data highlight the importance of miR-125a in the cell proliferation and progression of cervical cancer, and indicate that miR-125a may be a useful therapeutic target for cervical cancer.
引用
收藏
页码:25266 / 25280
页数:15
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