miR-454 suppresses the proliferation and invasion of ovarian cancer by targeting E2F6

Yunhe An; Jun Zhang; Xiaoyan Cheng; Baoming Li; Yanjie Tian; Xiaoli Zhang; Fangqi Zhao

doi:10.1186/s12935-020-01300-0

miR-454 suppresses the proliferation and invasion of ovarian cancer by targeting E2F6

Cancer Cell Int. 2020 Jun 12:20:237. doi: 10.1186/s12935-020-01300-0. eCollection 2020.

Authors

Yunhe An¹, Jun Zhang², Xiaoyan Cheng¹, Baoming Li¹, Yanjie Tian¹, Xiaoli Zhang¹, Fangqi Zhao²

Affiliations

¹ Department of Biotechnology, Beijing Center for Physical and Chemical Analysis, No. 27 Xisanhuan North Road, Beijing, 100089 China.
² Department of Obstetrics and Gynecology, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029 China.

Abstract

Background: The aberrant expression of microRNA-454 (miR-454) has been confirmed to be involved in the development of cancers. However, the functional role of miR-454 in the progression of ovarian cancer remains unclear.

Methods: The expression of miR-454 in ovarian cancer cells and serum of ovarian cancer patients was detected by RT-PCR. CCK8, colony formation, transwell, and flow cytometry assays were conducted to assess the effects of miR-454 on ovarian cancer cell proliferation, migration, invasion, and apoptosis, respectively. Dual-luciferase reporter assay was used to confirm the targeting relationship between miR-454 and E2F6. The expression pattern of E2F6 in ovarian cancer tissues was detected using immunohistochemistry (IHC) assay. The relative expression of related proteins was examined using western blot analysis.

Results: miR-454 was markedly down-regulated by hypoxia in ovarian cancer cells. Compared with normal samples, the expression of miR-454 was up-regulated in the serum of ovarian cancer patients, and correlated with the clinicopathological stages of ovarian cancer. Next, we found that miR-454 overexpression inhibited the proliferation, migration and invasion of OVCAR3 and SKOV3 cells, as well as promoted apoptosis. In addition, the Akt/mTOR and Wnt/β-catenin signaling pathway were inhibited by miR-454 in ovarian cancer cells. Mechanically, bioinformatic analysis and dual-luciferase reporter assay confirmed that E2F6 was a direct target of miR-454 and negatively regulated by miR-454 in ovarian cancer cells. Moreover, IHC analysis showed that E2F6 was highly expressed in ovarian cancer tissues. Finally, we found that the increasing cell proliferation and migration triggered by E2F6 overexpression were abolished by miR-454 overexpression.

Conclusion: Taken together, these results highlight the role of miR-454 as a tumor suppressor in ovarian cancer cells by targeting E2F6, indicating that miR-454 may be a potential diagnostic biomarker and therapeutic target for ovarian cancer.

Keywords: E2F6; Growth; Metastasis; Ovarian cancer; miR-454.