Open Access

ARTICLE

miR-204 Regulates Cell Proliferation and Invasion by Targeting EphB2 in Human Cervical Cancer

Shanhong Duan^*, Ali Wu^†, Zhengyu Chen^‡, Yarong Yang^*, Liying Liu^*, Qi Shu^*

* Department of Gynecology, Shaanxi Nuclear Industry 215 Hospital, Xianyang, Shaanxi, P.R. China
† Department of Endoscopy, Shaanxi Nuclear Industry 215 Hospital, Xianyang, Shaanxi, P.R. China
‡ Department of Spine Surgery, The First People’s Hospital of Xianyang City, Xianyang, Shaanxi, P.R. China

Oncology Research 2018, 26(5), 713-723. https://doi.org/10.3727/096504017X15016337254641

Abstract

MicroRNAs (miRNAs) are small noncoding RNAs that are involved in human carcinogenesis and progression. miR-204 has been reported to be a tumor suppressor in several cancer types. However, the function and underlying molecular mechanism of miR-204 in cervical cancer (CC) are still unclear. In the present study, the expression level of miR-204 was measured using the qRT-PCR method in 30 paired CC clinical samples and in 6 CC cell lines. We found that the expression of miR-204 was significantly downregulated in CC tissues and cell lines compared to normal cervical tissues and cell line. miR-204 was overexpressed by transfection with the miR-204 mimic in HeLa and C33A cell lines in the following experiments. The results showed that overexpression of miR-204 dramatically suppressed cell proliferation, migration, and invasion, caused cell cycle arrest at the G₀/G₁ phase, promoted cell apoptosis in vitro, and inhibited tumor growth in vivo. Western blot results indicated that overexpressing miR-204 decreased the expressions of CDK2, cyclin E, MMP2, MMP9, Bcl2, whereas it enhanced Bax expression and suppressed the activation of the PI3K/AKT signaling pathways in CC cells. Ephrin type B receptor 2 (EphB2) was identified as a direct target of miR-204 in CC cells according to bioinformatics analysis and luciferase reporter assay. Furthermore, knockdown of EphB2 mimicked the inhibitory effect of miR-204 on the proliferation, invasion, and migration of CC cells. These findings suggested that miR-204 might serve as a tumor suppressor in the development of CC by directly targeting EphB2.

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