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

// Jie Li 1, 2, 3 , Jiaojiao Lu 1, 2 , Zhongxue Ye 4 , Xi Han 1, 2 , Xia Zheng 1, 2 , Huilian Hou 5 , Wei Chen 6 , Xu Li 1, 2 and Le Zhao 1, 2 1 Center for Translational Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China 2 Key Laboratory for Tumor Precision Medicine of Shaanxi Province, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China 3 Department of Gynecology and Obstetrics, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China 4 Department of Gynecology, Ningbo No. 2 Hospital, Ningbo, China 5 Department of Pathology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China 6 Center 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.