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Regulation of E2F Transcription Factor 3 by microRNA-152 Modulates Gastric Cancer Invasion and Metastasis

Authors Shi L, Zhu H, Shen Y, Dou X, Guo H, Wang P, Zhang S, Zhou L, Zou X

Received 23 November 2019

Accepted for publication 30 January 2020

Published 14 February 2020 Volume 2020:12 Pages 1187—1197

DOI https://doi.org/10.2147/CMAR.S239752

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Dr Ahmet Emre Eskazan


Liangliang Shi, 1–3,* Hao Zhu, 1–3,* Yonghua Shen, 1–3,* Xiaotan Dou, 1–3 Huimin Guo, 1–3 Pin Wang, 1–3 Shu Zhang, 1–3 Lin Zhou, 1–3 Xiaoping Zou 1–3

1Department of Gastroenterology, Drum Tower Clinical Medical College of Nanjing Medical University, Nanjing 210008, People’s Republic of China; 2Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, People’s Republic of China; 3Jiangsu Clinical Medical Center of Digestive Disease, Nanjing 210008, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Xiaoping Zou; Lin Zhou
Department of Gastroenterology, Nanjing Drum Tower Hospital, No. 321 Zhongshan Road, Nanjing 210008, People’s Republic of China
Tel +86 25-68182222
Fax +86 25-83304616
Email 13770771661@163.com; zhoulin1105@163.com

Background: The transcription factor, E2F transcription factor 3 (E2F3), has been proved to modulate metastasis in multiple human cancers. The present study was aimed to expound the function and specific mechanism of E2F3 in gastric cancer (GC) progression.
Materials and Methods: The expression of E2F3, microRNA-152 (miR-152) and PLK1 (polo-like kinase 1) in GC cell lines was detected by quantitative RT-PCR and Western blot. The roles of E2F3 and miR-152 in GC metastasis were classified using gain-of-function and loss-of-function assays. The miRNAs directly targeting E2F3 were identified by bioinformatics analysis and luciferase reporter experiment. Chromatin immunoprecipitation was carried out to reveal the correlation between E2F3 and PLK1.
Results: E2F3 expression was frequently up-regulated in GC tissues, and its high expression might imply poor prognosis. Downregulation of E2F3 restrained GC migration and invasion in vitro and in vivo. Interestingly, we proved that miR-152 was an upstream regulator of E2F3. Moreover, miR-152 reduced E2F3 expression by directly targeting its 3ʹ-UTR, and then modulated GC metastasis via polo-like kinase 1 (PLK1) mediated protein kinase B (AKT) and extracellular signal-regulated kinase (ERK) signals.
Conclusion: E2F3 plays a crucial role in GC progression and the newly discovered miR-152/E2F3/PLK1 axis provides a new underlying target for therapy of metastasis in GC patients.

Keywords: miR-152, E2F3, PLK1, metastasis, gastric cancer

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