Androgen receptor suppresses vasculogenic mimicry in hepatocellular carcinoma via circRNA7/miRNA7-5p/VE-cadherin/Notch4 signalling.
Androgen receptor suppresses vasculogenic mimicry in hepatocellular carcinoma via circRNA7/miRNA7-5p/VE-cadherin/Notch4 signalling.
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雄激素受体通过 circRNA7/miRNA7-5p/VE-cadherin/Notch4 信号传导抑制肝细胞癌中的血管生成拟态
DOI：
10.1111/jcmm.16022
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发表时间：
2020-12
影响因子：
5.3
通讯作者：
Lu J
中科院分区：
文献类型：
--
作者：
Bao S;Jin S;Wang C;Tu P;Hu K;Lu J
雄激素受体（AR）可以抑制晚期肝细胞癌（HCC）的侵袭和转移。血管生成拟态（VM）是肿瘤组织自我滋养的一种新的血管化模式，与肿瘤进展和转移相关。在这里，我们研究了AR对HCC中VM形成的影响及其机制。结果表明，AR可以下调环状RNA（circRNA）7，上调微小RNA（miRNA）7-5p，并抑制HCC中VM的形成。小发夹circR7（ShcircR7）可以逆转HCC中小干扰AR（shAR）对VM和VE-cadherin和Notch4表达增加的影响，而抑制miR-7-5p则可以阻止HCC中VM的形成。 HCC 中 AR 过表达 (oeAR) 降低了 VM 的表达以及 VE-cadherin 和 Notch4 的表达。机制剖析表明，AR可以直接靶向circR7宿主基因启动子来抑制circR7，而miR-7-5p可能直接靶向VE-cadherin和Notch4 3'UTR来抑制它们在HCC中的表达。此外，Notch4和/或VE-cadherin的敲低表明，单独的shVE-cadherin或shNotch4可以部分逆转HCC VM的形成，而shVE-cadherin和shNotch4一起可以完全抑制HCC VM的形成。这些结果表明，AR可以通过下调HCC中的circRNA7/miRNA7-5p/VE-Cadherin/Notch4信号来抑制HCC VM的形成，这将有助于设计针对HCC的新疗法。
Androgen receptor (AR) can suppress hepatocellular carcinoma (HCC) invasion and metastasis at an advanced stage. Vasculogenic mimicry (VM), a new vascularization pattern by which tumour tissues nourish themselves, is correlated with tumour progression and metastasis. Here, we investigated the effect of AR on the formation of VM and its mechanism in HCC. The results suggested that AR could down‐regulate circular RNA (circRNA) 7, up‐regulate micro RNA (miRNA) 7‐5p, and suppress the formation of VM in HCC Small hairpin circR7 (ShcircR7) could reverse the impact on VM and expression of VE‐cadherin and Notch4 increased by small interfering AR (shAR) in HCC, while inhibition of miR‐7‐5p blocked the formation of VM and expression of VE‐cadherin and Notch4 decreased by AR overexpression (oeAR) in HCC. Mechanism dissection demonstrated that AR could directly target the circR7 host gene promoter to suppress circR7, and miR‐7‐5p might directly target the VE‐cadherin and Notch4 3′UTR to suppress their expression in HCC. In addition, knockdown of Notch4 and/or VE‐cadherin revealed that shVE‐cadherin or shNotch4 alone could partially reverse the formation of HCC VM, while shVE‐cadherin and shNotch4 together could completely suppress the formation of HCC VM. Those results indicate that AR could suppress the formation of HCC VM by down‐regulating circRNA7/miRNA7‐5p/VE‐Cadherin/Notch4 signals in HCC, which will help in the design of novel therapies against HCC.
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影响因子：
9
作者：
Yang, Lian-Yue;Fang, Feng;Wu, Fan
通讯作者：
Wu, Fan
影响因子：
17.1
作者：
Wu MH;Ma WL;Hsu CL;Chen YL;Ou JH;Ryan CK;Hung YC;Yeh S;Chang C
通讯作者：
Chang C
影响因子：
8
作者：
Bai, Jian;Yeh, Shuyuan;Chang, Chawnshang
通讯作者：
Chang, Chawnshang
影响因子：
4.1
作者：
Kanda T;Yokosuka O
通讯作者：
Yokosuka O
EBV 相关上皮恶性肿瘤中血管生成拟态的形成
影响因子：
16.6
作者：
Xiang T;Lin YX;Ma W;Zhang HJ;Chen KM;He GP;Zhang X;Xu M;Feng QS;Chen MY;Zeng MS;Zeng YX;Feng L
通讯作者：
Feng L