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Abstract Title:

20(S)-Rg3 upregulates FDFT1 via reducing miR-4425 to inhibit ovarian cancer progression.

Abstract Source:

Arch Biochem Biophys. 2020 Aug 30:108569. Epub 2020 Aug 30. PMID: 32877662

Abstract Author(s):

Jiaojiao Lu, Yuanyuan Zhou, Xia Zheng, Lihong Chen, Xiaoqian Tuo, Hong Chen, Mei Xue, Qian Chen, Wei Chen, Xu Li, Le Zhao

Article Affiliation:

Jiaojiao Lu

Abstract:

We previously found that ginsenoside 20(S)-Rg3 diminishes the proliferative and invasive capacities of ovarian cancer cells by decreasing miR-4425 level. Yet the mechanism of action of miR-4425 in ovarian cancer remains unclear. Here we report that miR-4425 is upregulated in ovarian cancer tissues relative to normal ovarian tissues, and transfection of miR-4425 inhibitor impairs the proliferation, migration and invasion of SKOV3 and 3AO ovarian cancer cells. Further, miR-4425 antagomiR reduces cell proliferation in a subcutaneous SKOV3 xenograft model using BALB/c nude mice. We identified farnesyl-diphosphate farnesyltransferase 1 (FDFT1) as a direct target of miR-4425 by Western blotting and a luciferase reporter assay. Forced expression of FDFT1 via transfection of an FDFT1-expressing plasmid into ovarian cancer cells not only retards cell proliferation, motility and invasiveness, but also negates the tumorigenic properties of amiR-4425 mimic. By contrast, silencing of FDFT1 by siRNAs abrogates suppression of the proliferation, migration and invasion of ovarian cancer cells treated with amiR-4425 inhibitor. Finally, transfection of either miR-4425 mimic or FDFT1 siRNAs into 20(S)-Rg3-treated ovarian cancer cells counteracts the tumor-inhibitory activity of the ginsenoside. In conclusion, 20(S)-Rg3 exerts anti-ovarian cancer activity by downregulating oncogenic miR-4425 that inhibits the expression of the tumor suppressor gene FDFT1. These results expand our current understanding of the molecular pathways leading to ovarian cancer progression, and unveil the mechanism of action of 20(S)-Rg3 in ovarian cancer inhibition.

Study Type : Animal Study

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