Low Expression of miR-448 Induces EMT and Promotes Invasion by Regulating ROCK2 in Hepatocellular Carcinoma

Low Expression of miR-448 Induces EMT and Promotes Invasion by Regulating ROCK2 in Hepatocellular Carcinoma
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DOI:
10.1159/000430114
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发表时间:
2015-05-01
影响因子:
--
通讯作者:
Lu, Jun
Lu, Jun
中科院分区:
医学1区
文献类型:
--
作者:
Zhu, Huaqiang;Zhou, Xu;Lu, Jun

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背景/目标:miR-448在肝细胞癌(hepatocellular carcinoma,HCC)中表达异常,但其在HCC进展中的作用尚不清楚。方法:采用实时荧光定量PCR方法检测117例肝癌组织中miRNAs及候选基因的表达。在人HCC细胞中转染miR-448模拟物和抑制剂。transwell法检测细胞侵袭能力。荧光素酶报告基因检测证实了其调控机制。Western blot检测EMT标志物。结果:miR-448在HCC样本中减少,并与HCC的发展相关。抑制miR-448显著促进细胞侵袭,而上调miR-448的作用则相反,miR-448可调控肝癌中ROCK 2的表达。ROCK 2表达的敲低部分逆转了miR-448抑制剂的作用。miR-448的异常表达可调节上皮间质转化(EMT)标志物的表达。结论:miR-448可能通过调控ROCK 2的表达参与HCC的发生发展。
Background/Aims: miR-448 has been reported to exhibit abnormal expression in hepatocellular carcinoma (HCC), however, the essential role of miR-448 in HCC progression is still unclear. Methods: real-time PCR was used to detect the expression of miRNAs and candidate genes in HCC samples (n=117). miR-448 mimics and inhibitor were tansfected in human HCC cells. The transwell assay was used to examine the cell invasive ability. The regulation mechanism was confirmed by luciferase reporter assay. The markers of EMT were detected by using Western blot. Results: miR-448 was decreased in HCC samples and associated with HCC development. Inhibition of miR-448 significantly promoted cell invasion, while the effect of miR-448 up-regulation was reverse miR-448 could regulate ROCK2 in hepatocellular carcinoma. Knockdown of ROCK2 expression partially reversed the effect of miR-448 inhibitor. Abnormal expression of miR-448 could regulate the markers of epithelialmesenchymal transition (EMT). Conclusions: miR-448 may contribute to the progression of HCC via regulating ROCK2 expression.