Oncotarget

Research Papers:

20(S)-Rg3 blocked epithelial-mesenchymal transition through DNMT3A/miR-145/FSCN1 in ovarian cancer

Jie Li, Jiaojiao Lu, Zhongxue Ye, Xi Han, Xia Zheng, Huilian Hou, Wei Chen, Xu Li and Le Zhao _

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Oncotarget. 2017; 8:53375-53386. https://doi.org/10.18632/oncotarget.18482

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Abstract

Jie Li1,2,3, Jiaojiao Lu1,2, Zhongxue Ye4, Xi Han1,2, Xia Zheng1,2, Huilian Hou5, Wei Chen6, Xu Li1,2 and Le Zhao1,2

1Center for Translational Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China

2Key Laboratory for Tumor Precision Medicine of Shaanxi Province, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China

3Department of Gynecology and Obstetrics, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China

4Department of Gynecology, Ningbo No. 2 Hospital, Ningbo, China

5Department of Pathology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China

6Center for Laboratory Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China

Correspondence to:

Le Zhao, email: zhaole2@mail.xjtu.edu.cn

Xu Li, email: lixu56@mail.xjtu.edu.cn

Keywords: ovarian cancer, ginsenoside, microRNA, methylation, epithelial-mesenchymal transition

Received: August 20, 2016     Accepted: May 29, 2017     Published: June 15, 2017

ABSTRACT

Epithelial-mesenchymal transition (EMT) is one of the key mechanisms mediating cancer progression. MicroRNAs (miRs) are essential regulators of gene expression by suppressing translation or causing degradation of target mRNA. Growing evidence illustrates the crucial roles of miRs dysregulation in cancer development and progression. Here, we have found for the first time that the ginsenoside 20(S)-Rg3, a pharmacologically active component of Panax ginseng, potently increases miR-145 expression by downregulating methyltransferase DNMT3A to attenuate the hypermethylation of the promoter region in the miR-145 precursor gene. Restoration of DNMT3A reverses the inhibitory effect of 20(S)-Rg3 on EMT. FSCN1 is verified as the target of miR-145 to suppress EMT in human ovarian cancer cells. The results from nude mouse xenograft models further demonstrate the suppressive effect of miR-145 on malignant progression of ovarian cancer. Taken together, our results show that 20(S)-Rg3 blocks EMT by targeting DNMT3A/miR-145/FSCN1 pathway in ovarian cancer cells, highlighting the potentiality of 20(S)-Rg3 to be used as a therapeutic agent for ovarian cancer.


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