Suppression of epithelial-mesenchymal transition in hepatocellular carcinoma cells by Krüppel-like factor 4.
Suppression of epithelial-mesenchymal transition in hepatocellular carcinoma cells by Krüppel-like factor 4.
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Kruppel 样因子 4 对肝细胞癌细胞上皮间质转化的抑制。
DOI：
10.18632/oncotarget.8831
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发表时间：
2016-05-17
期刊：
影响因子：
--
通讯作者：
Wang L
中科院分区：
文献类型：
--
作者：
Li Q;Song W;Wang W;Yao S;Tian C;Cai X;Wang L
肝细胞癌（HCC）是最恶性和最致命的人类癌症之一。上皮-间质转化（Epithelial-mesenchymal transition， EMT）促进了HCC的癌变，针对EMT的治疗似乎是有希望的治疗方法。我们之前已经证明kr<s:1> ppel样因子4 （KLF4）通过下调EMT相关蛋白抑制HCC细胞的EMT。在这里，我们研究了microrna （mirna）在HCC细胞中klf4调控的EMT中的作用。KLF4诱导3种mirna （miR-153， miR-506和miR-200b）分别靶向Snail1， Slug和ZEB1 mrna的3 ' -UTR，从而抑制HCC细胞中的蛋白翻译，通过启动子荧光素酶实验证实了这一点。任何一种miRNA的表达均能显著抑制HCC细胞的生长和侵袭性，而3种miRNA联合表达的效果更为明显。此外，这3种mirna的反义过表达可消除KLF4对HCC细胞生长和侵袭性的抑制作用。总之，我们的数据表明KLF4抑制emt增强的HCC生长和侵袭，可能是通过增加miR-153、miR-506和miR-200b来减少emt相关蛋白Snail1、Slug和ZEB1。
Hepatocellular carcinoma (HCC) is one of the most malignant and lethal human cancers. Epithelial-mesenchymal transition (EMT) enhances the carcinogenesis of HCC, and therapies targeting EMT appear to be promising treatments. We have previously shown that Krüppel-like Factor 4 (KLF4) suppressed EMT of HCC cells through downregulating EMT-associated proteins. Here, we examined the roles of microRNAs (miRNAs) in KLF4-regulated EMT in HCC cells. KLF4 induced expression of 3 miRNAs (miR-153, miR-506 and miR-200b) that targeted 3′-UTR of Snail1, Slug and ZEB1 mRNAs, respectively, to inhibit protein translation in HCC cells, which was confirmed by promoter luciferase assay. Expression of either miRNA significantly inhibited HCC cell growth and invasiveness, while the effect of combined expression of all 3 miRNAs was more pronounced. Furthermore, overexpression of antisense of all 3 miRNAs abolished the inhibitory effect of KLF4 on HCC cell growth and invasiveness. Together, our data suggest that KLF4 inhibits EMT-enhanced HCC growth and invasion, possibly through reducing EMT-related proteins Snail1, Slug and ZEB1 via increasing miR-153, miR-506 and miR-200b.
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