MicroRNA-18a suppresses ovarian carcinoma progression by targeting CBX7 and regulating ERK/MAPK signaling pathway and epithelial-to-mesenchymal transition

Y. Zhao, X.-L. Liu, J.-H. Huang, A.-J. Yin, H. Zhang

Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan, Shandong, China. wiazivd@163.com

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• Oncology

OBJECTIVE: Ovarian carcinoma (OC) is one prevalent fatal malignancy in gynecology. Currently, there is an imperative need to better investigate the pathogenesis of OC. Accumulating evidence has indicated that microRNAs (miRNAs) play pivotal roles in OC occurrence and development. In this study, we mainly investigated the potential roles of miR-18a in OC progression.

PATIENTS AND METHODS: We first examined miR-18a expressions in OC tissue samples and cell lines using quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Moreover, OC patients involved in current study were assigned into two groups based on the mean miR-18a expression level. Kaplan-Meier analysis was carried out to assess the overall survival rate of miR-18a in OC patients. Next, we investigated whether miR-18a could regulate OC cell proliferation abilities by using MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide) assays. Next, transwell assay was used to detect the effects of miR-18a on cell invasion and migration. We further performed Luciferase reporter assays by cotransfecting with miR-18a mimics and the Luciferase reporter vector containing CBX7 3’UTR-WT or MUT. We then performed immunohistochemistry (IHC) assays to determine the expression of CBX7 in OC tissues.

RESULTS: QRT-PCR results indicated that miR-18a expressions were notably decreased in OC related cell lines and tissues. Moreover, the low miR-18a expression was related to the malignant phenotype and poor prognosis of OC patients. Overexpression of miR-18a in OC cells could prominently suppress the proliferation, migration and invasion abilities via modulating ERK/MAPK pathway and epithelial-to-mesenchymal transition (EMT). Furthermore, CBX7 was confirmed as a functional target of miR-18a, indicating that miR-18a exerted the suppressive functions in OC cells partially via the regulation of CBX7. Additionally, restoration of miR-18a remarkably reduced the OC tumor growth in vivo.

CONCLUSIONS: Taken together, our study rationally suggested that miR-18a may serve as an effective diagnostic and therapeutic biomarker for OC.

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