Cell death & disease · 2018
The activation of microRNA-520h-associated TGF-β1/c-Myb/Smad7 axis promotes epithelial ovarian cancer progression.
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Zhang Jing, Liu Wenxue, Shen Fangqian, Ma Xiaoling, Liu Xiaorui, Tian Fuju, Zeng Weihong, Xi Xiaowei, Lin Yi
Аннотация
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.
Предметные рубрики MeSH
AnimalsCarcinoma, Ovarian EpithelialCell Line, TumorCell MovementCell ProliferationDisease ProgressionDown-RegulationEpithelial-Mesenchymal TransitionFemaleGene Expression Regulation, NeoplasticHumansMiceMice, Inbred BALB CMice, NudeMicroRNAsNeoplasm InvasivenessOvarian NeoplasmsPrognosisProto-Oncogene Proteins c-mybSmad7 ProteinTransforming Growth Factor beta1Up-Regulation