miR-224 promotion of cell migration and invasion by targeting Homeobox D 10 gene in human hepatocellular carcinoma
miR-224 promotion of cell migration and invasion by targeting Homeobox D 10 gene in human hepatocellular carcinoma
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miR-224通过靶向Homeobox D 10基因促进人肝细胞癌细胞迁移和侵袭
DOI：
10.1111/jgh.12429
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发表时间：
2014-04-01
影响因子：
4.1
通讯作者：
Wang, Ge
中科院分区：
文献类型：
--
作者：
Li, Qiong;Ding, Chenchen;Wang, Ge
micrornas （miRNAs）是一种小的非编码RNA分子，可控制靶基因的表达，并参与多种细胞通路的调控。在我们之前的研究中，我们已经证明miR-224在肝癌细胞和组织中过表达，是调控细胞迁移和侵袭的重要因素。本研究旨在进一步探讨miR-224在肝癌细胞迁移和侵袭中的调控机制。方法荧光素酶报告基因法证实HOXD10基因是miR-224的直接靶基因。通过定量逆转录聚合酶链反应、Western blotting、Transwell迁移和Matrigel侵袭实验，阐明miR-224在人肝细胞癌（HCC）中调控细胞迁移和侵袭的分子机制。结果(i) miR-224在MHHC97H和MHCC97L细胞中表达强烈上调，其表达水平与细胞侵袭电位显著相关。（ii） HOXD10基因被证实是miR-224的直接靶点。与正常肝组织和细胞相比，HOXD10在HCC组织和细胞中的表达较低，并负调控HCC细胞的侵袭。（iii） miR-224通过直接靶向HOXD10促进肿瘤侵袭相关蛋白p-PAK4和MMP-9的表达。我们的研究结果提示了先前未被描述的miR-224/HOXD10/p-PAK4/MMP-9信号通路参与细胞迁移和侵袭的调控，并为HCC治疗提供了新的生物靶点。
Background and AimMicroRNAs (miRNAs) are small noncoding RNA molecules that control target gene expression and are implicated in the regulation of diverse cellular pathways. In our previous research, we have demonstrated that miR-224 was overexpressed in liver cancer cells and tissues, which was an important factor in the regulation of cell migration and invasion. This study aimed to further explore the regulatory mechanism of miR-224 in the migration and invasion in liver cancer cells.MethodsA luciferase reporter assay was used to confirm that the HOXD10 gene was a direct target of miR-224. Quantitative reverse transcriptase-polymerase chain reaction, Western blotting, Transwell migration, and Matrigel invasion assays were performed to clarify the molecular mechanism of miR-224 in the regulation of cell migration and invasion in human hepatocellular carcinoma (HCC).Results(i) The expression of miR-224 was strongly upregulated in MHHC97H and MHCC97L cells, and its expression level was significantly associated with cell invasive potential. (ii) The HOXD10 gene was confirmed to be a direct target of miR-224. Compared with normal liver tissues and cells, HOXD10 had lower expression in HCC tissues and cells and inversely regulated HCC cell invasion. (iii) miR-224 promoted expression of the tumor invasion-associated proteins p-PAK4 and MMP-9 by directly targeting HOXD10.ConclusionOur findings suggest a previously undescribed regulatory pathway in which the miR-224/HOXD10/p-PAK4/MMP-9 signaling pathway contributes to the regulation of cell migration and invasion and provides a new biotarget for HCC treatment.