The activation of microRNA-520h-associated TGF-β1/c-Myb/Smad7 axis promotes epithelial ovarian cancer progression.
The activation of microRNA-520h-associated TGF-β1/c-Myb/Smad7 axis promotes epithelial ovarian cancer progression.
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microRNA-520h 相关 TGF-β1/c-Myb/Smad7 轴的激活促进上皮性卵巢癌进展。
DOI：
10.1038/s41419-018-0946-6
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发表时间：
2018-08-29
影响因子：
9
通讯作者：
Lin Y
中科院分区：
文献类型：
--
作者：
Zhang J;Liu W;Shen F;Ma X;Liu X;Tian F;Zeng W;Xi X;Lin Y
在妇科癌症中，上皮性卵巢癌（EOC）由于肿瘤进展和转移的高发生率而具有最高的致死率。探讨卵巢上皮癌转移的详细机制和关键靶点的确定对于更好地估计预后和改善治疗具有重要意义。本研究旨在明确miR-520 h在EOC患者预后中的作用及其参与EOC进展的机制。我们发现，miR-520 h在116例EOC患者中上调，尤其是在那些晚期疾病中，高miR-520 h表达预测预后不良。miR-520 h的异位表达可促进上皮性卵巢癌细胞的增殖、迁移和侵袭，并诱导上皮细胞向间质细胞转化。miR-520 h通过下调Smad 7并随后激活TGF-β信号通路促进EOC进展。最重要的是，TGF-β1刺激通过上调其转录因子c-Myb增加EOC细胞中miR-520 h的表达。总之，我们描述了TGF-β1/c-Myb/miR-520 h/Smad 7轴在EOC转移中的作用，并强调了miR-520 h作为EOC预后标志物的可能用途。
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.
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影响因子：
9
作者：
Amoroso MR;Matassa DS;Agliarulo I;Avolio R;Lu H;Sisinni L;Lettini G;Gabra H;Landriscina M;Esposito F
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DOI：
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发表时间：
2015-11
期刊：
Nature reviews. Cancer
影响因子：
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影响因子：
4
作者：
Kawaguchi H;Terai Y;Tanabe A;Sasaki H;Takai M;Fujiwara S;Ashihara K;Tanaka Y;Tanaka T;Tsunetoh S;Kanemura M;Ohmichi M
通讯作者：
Ohmichi M