期刊
ONCOTARGET
卷 8, 期 67, 页码 111258-111270出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.22770
关键词
microRNA-34a; Notch1; endometrial cancer; proliferation; invasion
资金
- National Natural Science Foundation of China [81571393]
- International Cooperation and Exchange Program of Shaanxi Province [2013KW27-02]
- Fundamental Research Funds for the Central Universities [2013JDHZ31]
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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