Emodin Inhibits TGF-β2 by Activating the FOXD3/miR‑199a Axis in Ovarian Cancer Cells In vitro

Overview

Journal Oncol Rep

Specialty Oncology

Date 2018 Mar 8

PMID 29512773

Citations 11

Authors

Kejuan Song

Teng Lv

Yulong Chen

Yuchao Diao

Qin Yao

Yankui Wang

Affiliations

Soon will be listed here.

Abstract

Ovarian cancer is a highly metastatic malignancy and a leading cause of cancer-related death in postmenopausal women. Emodin is a natural anthraquinone isolated from several traditional Chinese medicines including Rhubarb and Polygonum cuspidatum. Recently, emodin was demonstrated to reduce the growth of human ovarian carcinoma cells. However, the mechanism remains unclear. In the present study, we identified that transforming growth factor (TGF)-β2 was significantly affected by emodin treatment in A2780 cells using microarray analysis. MicroRNA (miR)-199a was predicted as a potential miRNA targeting TGF-β2 by in silico prediction using TargetScan. The mRNA and protein levels of TGF-β2 were both significantly reduced by miR-199a. Spearman's correlation analysis revealed a significant correlation between the expression level of miR-199a and TGF-β2 in human ovarian cancer specimens. Silencing of miR-199a with miR-199a inhibitor significantly restored the reduction in TGF-β2 expression induced by emodin. Additionally, cell viability and colony formation of A2780 cells were markedly inhibited by emodin treatment, which was mediated by miR-199a. We analyzed the primary mature miR-199a-1 and miR-199a-2 transcripts in A2780 cells treated with emodin or dimethyl sulfoxide (DMSO) and found that only pri-miR-199a-1 was regulated by emodin. A conserved binding site of Forkhead box D3 (FOXD3) was identified within pri-miR‑199a-1. We further revealed that miR-199a expression was significantly regulated by FOXD3. Taken together, the present study demonstrated that emodin may directly promote FOXD3 expression and sequentially activates miR-199a, which in turn suppresses the expression of TGF-β2 to reduce cell viability and colony formation of A2780 cells.

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