Department of Human Anatomy, Histology and Embryology, School of Biology and Basic Medical Sciences, Soochow University, Suzhou 215007, China.
School of Medicine, Yangzhou University, Yangzhou 225001, China.
Biomed Res Int. 2019 May 12;2019:4371405. doi: 10.1155/2019/4371405. eCollection 2019.
MicroRNAs (MiRNAs), which regulate the gene expression leading to translational inhibition or mRNA degradation, are involved in carcinogenesis and tumor progression. Previous studies have demonstrated that miR-221 was one of the most consistent overexpressed miRNAs in several types of cancer. However, the role of miR-221 in human liver cancer progression is not yet fully elucidated. Levels of miR-221 and plant homeodomain finger 2 (PHF2) expressions in human hepatocellular carcinoma (HCC) tissues and cell lines were detected using western blotting and quantitative real-time PCR (qRT-PCR). Cell migration was studied using the transwell assays. A dual-luciferase reporter system was used to validate the target gene of miR-221. The results indicated that miR-221 promoted HCC cell migration. By performing subsequent systematic bioinformatic analyses, we found PHF2 was the target gene of miR-221 and the direct binding relationship was further validated by dual-luciferase reporter assay. In addition, lower expression of PHF2 promoted HCC cell migration and linked to worse overall survival in HCC patients. Finally, the negative correlation between miR-221 and PHF2 expression levels in HCC specimens was further confirmed. Taken together, our findings implied that miR-221 could be a potential candidate for the therapeutics of HCC metastasis.
微小 RNA（miRNAs）通过调控导致翻译抑制或 mRNA 降解的基因表达，参与了癌症的发生和肿瘤的进展。先前的研究表明，miR-221 是几种类型癌症中最一致过表达的 miRNA 之一。然而，miR-221 在人类肝癌进展中的作用尚未完全阐明。通过 Western blot 和定量实时 PCR（qRT-PCR）检测人肝癌（HCC）组织和细胞系中 miR-221 和植物同源域指 2（PHF2）的表达水平。使用 Transwell 测定法研究细胞迁移。双荧光素酶报告系统用于验证 miR-221 的靶基因。结果表明，miR-221 促进了 HCC 细胞迁移。通过进行后续的系统生物信息学分析，我们发现 PHF2 是 miR-221 的靶基因，双荧光素酶报告实验进一步验证了这种直接的结合关系。此外，PHF2 的低表达促进了 HCC 细胞迁移，并与 HCC 患者的总体生存率降低相关。最后，进一步证实了 HCC 标本中 miR-221 和 PHF2 表达水平之间的负相关关系。总之，我们的研究结果表明，miR-221 可能是 HCC 转移治疗的潜在候选物。
