Yu Lei, Ding Guo-feng, He Changzhi, Sun Lei, Jiang YanFang, Zhu Liying
Department of Infectious Disease, The Fourth Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
Department of Infectious Disease, Binzhou Medical University Hospital, Binzhou, Shandong, China.
PLoS One. 2014 Mar 27;9(3):e91661. doi: 10.1371/journal.pone.0091661. eCollection 2014.
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide. MicroRNAs (miRNAs) are important regulators of multiple cellular processes, and the aberrant miRNAs expressions have been observed in different types of cancer including HCC. Their pathysiologic role and their relevance to tumorigenesis are still largely unknown. In this study, we demonstrated the down-regulation of miR-424 in HCC cell lines and tissues by quantitative RT-PCR analyses. Overexpression of miR-424 reduced the HCC cell prolifetation, migration, and invasion. Conversely, inhibiton of miR-424 expression significantly accelerated the cell proliferation, migration, and invasion. In addition, we further identified c-Myb as a functional downstream target of miR-424 by directly targeting the 3'UTR of c-Myb. Furthermore, overexpression of c-Myb impaired miR-424-induced inhibition of proliferation and invasion in HCC cells. Our results demonstrated that miR-424 was involved in tumorigenesis of HCC at least in part by suppression of c-Myb.
肝细胞癌（HCC）是全球癌症相关死亡的主要原因之一。微小RNA（miRNA）是多种细胞过程的重要调节因子，在包括HCC在内的不同类型癌症中均观察到miRNA表达异常。它们的生理作用及其与肿瘤发生的相关性仍大多未知。在本研究中，我们通过定量RT-PCR分析证明了miR-424在HCC细胞系和组织中的表达下调。miR-424的过表达降低了HCC细胞的增殖、迁移和侵袭能力。相反，抑制miR-424表达显著加速了细胞增殖、迁移和侵袭。此外，我们通过直接靶向c-Myb的3'UTR进一步确定c-Myb是miR-424的功能性下游靶点。此外，c-Myb的过表达削弱了miR-424诱导的对HCC细胞增殖和侵袭的抑制作用。我们的结果表明，miR-424至少部分通过抑制c-Myb参与了HCC的肿瘤发生。
