title: MiR-125a suppresses tumor growth, invasion and metastasis in cervical cancer by targeting STAT3.
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.
authors.affiliation: Department of Oncology, PLA General Hospital, Beijing, China.
authors.forename: Zhongyi
authors.initials: Z
authors.lastname: Fan
authors.affiliation: Department of Oncology, 309th Hospital of PLA, Beijing, China.
authors.forename: Hanzhi
authors.initials: H
authors.lastname: Cui
authors.affiliation: Department of Medical Molecular Biology, Beijing Institute of Biotechnology, Beijing, China.
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Oncology, PLA General Hospital, Beijing, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Lin
authors.affiliation: Department of Oncology, PLA General Hospital, Beijing, China.
authors.forename: Xuelin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Nuclear Medicine, Peking University First Hospital, Beijing, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Kang
authors.affiliation: Department of Endocrinology and Metablism, 264th Hospital of PLA, Shanxi, China.
authors.forename: Baiyu
authors.initials: B
authors.lastname: Han
authors.affiliation: Department of Oncology, PLA General Hospital, Beijing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Meng
authors.affiliation: Department of Oncology, PLA General Hospital, Beijing, China.
authors.forename: Zhifeng
authors.initials: Z
authors.lastname: Yan
authors.affiliation: Department of Oncology, PLA General Hospital, Beijing, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Yan
authors.affiliation: Department of Oncology, PLA General Hospital, Beijing, China.
authors.forename: Shunchang
authors.initials: S
authors.lastname: Jiao
mesh_terms: D020413:3' Untranslated Regions; D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000556:secondary / Q000628:therapy / Q000821:virology; D000818:Animals; D001665:Binding Sites; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000556:secondary / Q000628:therapy / Q000821:virology; D002465:Cell Movement; D049109:Cell Proliferation; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D059565:G2 Phase Cell Cycle Checkpoints; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D006801:Humans; D053208:Kaplan-Meier Estimate; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D027383:Papillomaviridae / Q000472:pathogenicity; D011485:Protein Binding; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D016896:Treatment Outcome; D047368:Tumor Burden; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000628:therapy / Q000821:virology
chemical_list: D020413:3' Untranslated Regions; C531888:MIRN125 microRNA, human; D035683:MicroRNAs; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53
keywords: STAT3; cell growth; cervical cancer; metastasis; miR-125a