State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China.
Shanghai High-Tech United Bio-Technological R&D Co, Ltd, Shanghai, China.
J Cell Biochem. 2018 Nov;119(11):9229-9238. doi: 10.1002/jcb.27190. Epub 2018 Jun 28.
Mature microRNAs (miRNAs) are a class of small noncoding RNA molecules involved in regulation of post-translational gene expression. Although aberrant levels of miRNAs have been found in various tumor tissues, their importance in tumor development and the molecular basis of their regulatory role remain unclear. Our bioinformatic analysis on The Cancer Genome Atlas database and microarray-based comparison of miRNA in different cell lines revealed that the level of mir-1287 is suppressed in hepatocellular carcinoma (HCC) cells. When upregulated, mir-1287 can reduce the tumorigenesis phenotypes of HCC cells in several in vitro models. We further found that mir-1287 directly targets messenger RNA encoding PIK3R3, which is a tumor-promoting factor acting in several pathways linked to tumorigenesis. Our study suggests that aberrant suppression of mir-1287 is potentially responsible for the development of HCC, and miRNA-based strategies may be developed for efficient detection and treatment of HCC.
成熟的 microRNAs(miRNAs)是一类参与调节翻译后基因表达的小非编码 RNA 分子。虽然在各种肿瘤组织中发现了异常水平的 miRNAs,但它们在肿瘤发生发展中的重要性及其调节作用的分子基础仍不清楚。我们对 The Cancer Genome Atlas 数据库的生物信息学分析和不同细胞系中 miRNA 的基于微阵列的比较表明,miR-1287 的水平在肝癌(HCC)细胞中受到抑制。当上调时,miR-1287 可以在几种体外模型中降低 HCC 细胞的肿瘤发生表型。我们进一步发现,miR-1287 可以直接靶向编码 PIK3R3 的信使 RNA,PIK3R3 是一种促进肿瘤的因子,作用于与肿瘤发生相关的几个途径。我们的研究表明,miR-1287 的异常抑制可能是 HCC 发生的原因,并且可能开发基于 miRNA 的策略来有效检测和治疗 HCC。