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Oncotarget. 2015 Sep 22;6(28):25266-80. doi: 10.18632/oncotarget.4457.

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

Author information

1
Department of Oncology, PLA General Hospital, Beijing, China.
2
Department of Oncology, 309th 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, 264th Hospital of PLA, Shanxi, China.

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.

KEYWORDS:

STAT3; cell growth; cervical cancer; metastasis; miR-125a

PMID:
26389681
PMCID:
PMC4694830
DOI:
10.18632/oncotarget.4457
[Indexed for MEDLINE]
Free PMC Article

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