miR-498 inhibits the growth and metastasis of liver cancer by targeting ZEB2
miR-498 inhibits the growth and metastasis of liver cancer by targeting ZEB2
复制标题
miR-498通过靶向ZEB2抑制肝癌的生长和转移
DOI：
10.3892/or.2018.6948
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发表时间：
2019-03-01
期刊：
影响因子：
4.2
通讯作者：
Xu, Wenrong
中科院分区：
文献类型：
--
作者：
Zhang, Xu;Xu, Xueying;Xu, Wenrong
微小RNA（microRNAs，miRNAs）在肝癌的生长、转移和耐药中起着重要作用。越来越多的证据表明，miR-498在几种人类恶性肿瘤中异常表达。然而，miR-498在肝癌中的作用和潜在机制仍不清楚。在本研究中，我们探讨了miR-498在肝癌中的潜在作用和临床价值。我们发现miR-498在肝癌患者组织中的表达水平显著低于健康对照组织。与正常人正常肝细胞系相比，肝癌细胞系中miR-498的表达也降低。miR-498过表达可明显抑制肝癌细胞的增殖、迁移和侵袭。miR-498过表达诱导肝癌细胞周期阻滞和凋亡，同时抑制上皮间质转化（EMT）。生物信息学分析和荧光素酶报告基因分析进一步鉴定了锌指E-box结合同源框2（ZEB 2）作为miR-498的新靶点。此外，ZEB 2敲低重现了肝癌细胞中miR-498过表达的抑制作用。ZEB 2过表达挽救了miR-498对肝癌细胞增殖、迁移和侵袭的抑制，表明ZEB 2在肝癌细胞中充当miR-498的下游效应子。因此，我们证明了miR-498至少部分地通过直接靶向ZEB 2抑制肝癌细胞的生长和转移，这表明miR-498可以作为肝癌诊断和治疗的潜在生物标志物。
MicroRNAs (miRNAs) play critical roles in the growth, metastasis and therapeutic resistance of liver cancer. Accumulating evidence suggests that miR-498 is aberrantly expressed in several human malignancies. However, the role and underlying mechanism of miR-498 in liver cancer remain unclear. In the present study, we investigated the potential roles and clinical value of miR-498 in liver cancer. We found that the miR-498 expression level was significantly lower in liver cancer patient tissues than that in healthy control tissues. The expression of miR-498 was also decreased in liver cancer cell lines compared to that noted in a normal human normal liver cell line. miR-498 overexpression markedly inhibited liver cancer cell proliferation, migration and invasion. miR-498 overexpression induced cell cycle arrest and apoptosis while it suppressed epithelial-mesenchymal transition (EMT) in liver cancer cells. Bioinformatic analysis and luciferase reporter assay further identified zinc finger E-box binding homeobox 2 (ZEB2) as a novel target of miR-498. Furthermore, ZEB2 knockdown recapitulated the inhibitory effects of miR-498 overexpression in liver cancer cells. ZEB2 overexpression rescued the inhibition of liver cancer cell proliferation, migration, and invasion by miR-498, indicating that ZEB2 acts as a downstream effector of miR-498 in liver cancer cells. Thus, we demonstrated that miR-498 suppresses the growth and metastasis of liver cancer cells, partly at least, by directly targeting ZEB2, suggesting that miR-498 may serve as a potential biomarker for the diagnosis and therapy of liver cancer.