Oncotarget

Research Papers:

MicroRNA-34a inhibits cells proliferation and invasion by downregulating Notch1 in endometrial cancer

Zhen Wang, Wei Wang, Kangrong Huang, Yueling Wang, Jing Li and Xinyuan Yang _

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Oncotarget. 2017; 8:111258-111270. https://doi.org/10.18632/oncotarget.22770

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Abstract

Zhen Wang1,4,*, Wei Wang2,*, Kangrong Huang1, Yueling Wang1, Jing Li3 and Xinyuan Yang1

1Department of Gynecology and Obstetrics, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, P. R. China

2Department of Anesthesiology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, P. R. China

3Center for Translational Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, P. R. China

4Department of Gynecology and Obstetrics, Northwest Women’s and Children’s Hospital, Xi’an 710003, P. R. China

*Zhen Wang and Wei Wang contributed equally to this work and should be considered co-first authors

Correspondence to:

Xinyuan Yang, email: m18991232845 @163.com

Keywords: microRNA-34a; Notch1; endometrial cancer; proliferation; invasion

Received: August 21, 2017    Accepted: September 20, 2017    Published: November 30, 2017

ABSTRACT

MicroRNAs (miRNAs) are small non-coding RNAs composed of 18-25 nucleotides that regulate the expression of approximately 30% of human protein coding genes. Dysregulation of miRNAs plays a pivotal role in the initiation and progression of malignancies. Our study has shown that microRNA-34a (miR-34a) was upregulated in human endometrial cancer stem cells (ECSCs). However, it is unknown how miR-34a regulates endometrial cancer itself. Here, we report that miR-34a directly and functionally targeted Notch1. MiR-34a inhibited the proliferation, migration, invasion, EMT-associated phenotypes by downregulating Notch1 in endometrial cancer cells. Overexpression of miR-34a also suppressed tumor growth in nude mice. Importantly, further results suggested miR-34a was significantly downregulated in endometrial cancer tissues and negatively correlated with Notch1 expression. There was a significant association between decreased miR-34a expression and worse patient prognosis. Taken together, our results suggest that miR-34a plays tumor-suppressive roles in endometrial cancer through downregulating Notch1. Thus miR-34a could be a potential therapeutic target for prevention and treatment of endometrial cancer.


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