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

// Zhongyi Fan 1, * , Hanzhi Cui 2, * , Xiaojie Xu 3, * , Zhi Lin 1 , Xuelin Zhang 1 , Lei Kang 4 , Baiyu Han 5 , Jing Meng 1 , Zhifeng Yan 1 , Xiang Yan 1 , Shunchang Jiao 1 1 Department of Oncology, PLA General Hospital, Beijing, China 2 Department of Oncology, 309 th Hospital of PLA, Beijing, China 3 Department of Medical Molecular Biology, Beijing Institute of Biotechnology, Beijing, China 4 Department of Nuclear Medicine, Peking University First Hospital, Beijing, China 5 Department of Endocrinology and Metablism, 264 th Hospital of PLA, Shanxi, China * These authors have contributed equally to this work Correspondence to: Shunchang Jiao, e-mail: jiaosc301@163.com Keywords: miR-125a, cervical cancer, cell growth, metastasis, STAT3 Received: March 23, 2015      Accepted: June 30, 2015      Published: July 13, 2015 ABSTRACT 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.