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Journal of Ovarian Research
Published in: Journal of Ovarian Research 1/2019

Open Access 01-12-2019 | Ovarian Cancer | Research

MiR-203a-3p regulates the biological behaviors of ovarian cancer cells through mediating the Akt/GSK-3β/Snail signaling pathway by targeting ATM

Authors: Hong-Yun Liu, Yu-Ying Zhang, Bao-Lian Zhu, Fu-Zhong Feng, Hai-Tang Zhang, Hua Yan, Bin Zhou

Published in: Journal of Ovarian Research | Issue 1/2019

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Abstract

Objective

To investigate whether miR-203a-3p can regulate the biological behaviors of ovarian cancer cells by targeting ATM to affect the Akt/GSK-3β/Snail signaling pathway.

Methods

The expression levels of miR-203a-3p and ATM were detected by qRT-PCR, immunohistochemical staining and Western blotting in ovarian cancer tissues and adjacent normal tissues obtained from 152 subjects. A dual-luciferase reporter gene assay was performed to verify the relationship between miR-203a-3p and ATM. Human ovarian cancer cell lines (A2780 and SKOV3) were used to generate the Blank, miR-NC, miR-203a-3p mimic, Control siRNA, ATM siRNA, and miR-203a-3p inhibitor + ATM siRNA groups. The biological behaviors of ovarian cancer cells were evaluated by CCK-8, wound healing, and Transwell invasion assays, annexin V-FITC/PI staining and flow cytometry. The levels of Akt/GSK-3β/Snail pathway-related proteins were assessed by Western blotting.

Results

Ovarian cancer tissues showed lower miR-203a-3p levels and higher ATM levels than adjacent normal tissues, both of which were associated with the FIGO stage, grade and prognosis of ovarian cancer. As confirmed by a dual-luciferase reporter gene assay, miR-203a-3p could target ATM. Furthermore, the miR-203a-3p mimic had multiple effects, including the inhibition of the proliferation, invasion and migration of A2780 and SKOV3 cells, the promotion of cell apoptosis, the arrest of the cell cycle at the G1 phase, and the blockage of the Akt/GSK-3β/Snail signaling pathway. ATM siRNA had similar effects on the biological behaviors of ovarian cancer cells, and these effects could be reversed by a miR-203a-3p inhibitor.

Conclusion

miR-203a-3p was capable of hindering proliferation, migration, and invasion and facilitating the apoptosis of ovarian cancer cells through its modulation of the Akt/GSK-3β/Snail signaling pathway by targeting ATM, and therefore it could serve as a potential therapeutic option for ovarian cancer.
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Metadata
Title
MiR-203a-3p regulates the biological behaviors of ovarian cancer cells through mediating the Akt/GSK-3β/Snail signaling pathway by targeting ATM
Authors
Hong-Yun Liu
Yu-Ying Zhang
Bao-Lian Zhu
Fu-Zhong Feng
Hai-Tang Zhang
Hua Yan
Bin Zhou
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Journal of Ovarian Research / Issue 1/2019
Electronic ISSN: 1757-2215
DOI
https://doi.org/10.1186/s13048-019-0532-2

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