Targeting the estrogen receptor alpha (ERα)-mediated circ-SMG1.72/miR-141-3p/Gelsolin signaling to better suppress the HCC cell invasion
Targeting the estrogen receptor alpha (ERα)-mediated circ-SMG1.72/miR-141-3p/Gelsolin signaling to better suppress the HCC cell invasion
复制标题
靶向雌激素受体α (ERα) 介导的 circ-SMG1.72/miR-141-3p/Gelsolin 信号传导以更好地抑制 HCC 细胞侵袭。
DOI：
10.1038/s41388-019-1150-6
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发表时间：
2020-01-29
期刊：
影响因子：
8
通讯作者：
Yeh, Shuyuan
中科院分区：
文献类型：
--
作者：
Xiao, Yao;Liu, Guodong;Yeh, Shuyuan
早期研究表明雌激素受体α（ER α）可能影响肝细胞癌（HCC）的进展。然而，详细的机制，特别是其与凝溶胶蛋白（GSN）介导的细胞侵袭的联系仍不清楚。我们发现ER α可以通过抑制环状RNA-SMG1. 72来降低HCC细胞的侵袭性结果表明，ER α抑制的circ-SMG1. 72可以通过直接结合到其宿主基因SMG1的5 '启动子区来进行转录调控，从而海绵化和抑制microRNA的表达（miRNA，miR），miR-141 - 3p，其然后可以通过减少miR与其3 '非翻译区（3'UTR）的结合而导致GSN信使RNA翻译增加。使用肝癌细胞原位异种移植体内小鼠模型的临床前研究证实了体外数据，人类肝癌临床样本调查和组织染色也证实了ER alpha/miR-141 - 3 p/GSN信号传导与肝癌进展的联系。总之，我们的研究结果表明，ER alpha可以通过改变ER alpha/circRNA-SMG1. 72/miR-141 - 3p/GSN信号转导来抑制HCC细胞侵袭，并且用小分子靶向这种新发现的信号转导可能有助于开发新的治疗方法，以更好地抑制HCC进展。
Early studies indicated that estrogen receptor alpha (ER alpha) might impact the progression of hepatocellular carcinoma (HCC). However, the detailed mechanisms, especially its linkage to the gelsolin (GSN)-mediated cell invasion, remain unclear. Here we found that ER alpha could decrease HCC cell invasion via suppressing the circular RNA-SMG1.72 (circRNA-SMG1.72) expression via transcriptional regulation through directly binding to the 5 ' promoter region of its host gene SMG1, We showed that ER alpha-suppressed circ-SMG1.72 could sponge and inhibit the expression of the microRNA (miRNA, miR), miR-141-3p, which could then result in increasing the GSN messenger RNA translation via reduced miR binding to its 3 ' untranslated region (3 ' UTR). The preclinical study using an in vivo mouse model with orthotopic xenografts of HCC cells confirmed the in vitro data, and the human HCC clinical sample survey and tissue staining also confirmed the linkage of ER alpha/miR-141-3p/GSN signaling to the HCC progression. Together, our findings suggest that ER alpha can suppress HCC cell invasion via altering the ER alpha/circRNA-SMG1.72/miR-141-3p/GSN signaling, and targeting this newly identified signaling with small molecules may help in the development of novel therapies to better suppress the HCC progression.