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