The activation of microRNA-520h\u2013associated TGF-\u03b21/c-Myb/Smad7 axis promotes epithelial ovarian cancer progression

Jing Zhang,Fuju Tian,Weihong Zeng,Yi Lin,Fangqian Shen,Xiaoling Ma,Xiaorui Liu,Xiaowei Xi,Wenxue Liu

doi:10.1038/s41419-018-0946-6

Abstract

Among the gynaecological cancers, epithelial ovarian cancer (EOC) has the highest lethality because of the high incidence of tumour progression and metastasis. Exploration of the detailed mechanisms underlying EOC metastasis and the identification of crucial targets is important to better estimate the prognosis and improve the treatment of this disease. The present study aimed to identify the role of miR-520h in the prognosis of patients with EOC, and the mechanisms of its involvement in EOC progression. We showed that miR-520h was upregulated in 116 patients with EOC, especially in those with advanced-stage disease, and high miR-520h expression predicted poor outcome. Furthermore, ectopic expression of miR-520h enhanced EOC cell proliferation, migration and invasion, and induced epithelial–mesenchymal transition in vitro and in vivo. miR-520h promoted EOC progression by downregulating Smad7, and subsequently activating the TGF-β signalling pathway. Most importantly, TGF-β1 stimulation increased miR-520h expression in EOC cells by upregulating its transcription factor c-Myb. In conclusion, we described the role of the TGF-β1/c-Myb/miR-520h/Smad7 axis in EOC metastasis, and highlighted the possible use of miR-520h as a prognostic marker for EOC.

Highlights

Ovarian cancer is the leading cause of cancer-related death among the gynaecological cancers[1,2]
Results miR-520h is upregulated in Epithelial ovarian cancer (EOC) tissues and high miR-520h expression predicts poor survival To explore the clinical role of miR-520h, we first evaluated miR-520h expression in human tissues
In the present study, we demonstrated that miR-520h promotes EOC progression by regulating the TGF-β1/cMyb/Smad[7] axis, activation of which predicts poor prognosis for patients with EOC

Summary

Introduction

Ovarian cancer is the leading cause of cancer-related death among the gynaecological cancers[1,2]. Surgical techniques have improved and new targeted drugs are being used clinically, patients with advanced EOC only have 45% expected 5-year overall survival (OS), metastasis is complex, involving oncogene activation and tumour suppressor inactivation[7,8,9]. MicroRNAs (miRNAs) are non-coding 20–24 nucleotide long RNAs that can suppress gene expression by binding to the 3′ untranslated region (3′ UTR) of their target mRNAs and can be detected in the blood[10,11]. Aberrant miRNA expression might be involved in EOC progression and metastasis[16,17,18]. The miR-520 family contains several members that have been reported in human cancers.

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Results

Conclusion