Yan Shi-Yan, Chen Mei-Mei, Li Guang-Ming, Wang Yu-Qin, Fan Jian-Gao
Department of Gastroenterology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Repubic of China.
Tumour Biol. 2015 Jun;36(6):4747-55. doi: 10.1007/s13277-015-3124-9. Epub 2015 Feb 3.
MicroRNAs (miRNAs) regulate gene expression by inhibiting translation of target messenger RNAs (mRNAs) through pairing with miRNA recognition elements (MREs), usually in 3'-UTRs. miRNAs are involved in the pathogenesis of several types of cancers. Specifically, microRNA-32 (miR-32) is overexpressed in colorectal carcinoma, wherein accumulating evidence indicates that it functions as an oncogene. However, the function of miR-32 in hepatocellular carcinoma (HCC) has not been totally elucidated. In the present study, we found the expression of miR-32 was up-regulated in HCC tissue and cell lines, inversely the expression of phosphatase and tensin homolog (PTEN) decreased. Besides, miRNA-32 down-regulates PTEN through binding to 3'-UTR of PTEN mRNA from luciferase reporter assay, and the expression level of miR-32 could affect the proliferation, migration, and invasion of liver cancer cell lines via PTEN/Akt signaling pathway. Down-expression of PTEN could significantly attenuate the inhibitory effects of knockdown miR-32 on the proliferation, migration, and invasion of liver cancer cells, suggesting that miR-32 could be a potential target for HCC treatment.
微小RNA（miRNA）通过与通常位于3'-非翻译区（3'-UTR）的miRNA识别元件（MRE）配对，抑制靶信使核糖核酸（mRNA）的翻译，从而调控基因表达。miRNA参与多种类型癌症的发病机制。具体而言，微小RNA-32（miR-32）在结直肠癌中过表达，越来越多的证据表明它起着癌基因的作用。然而，miR-32在肝细胞癌（HCC）中的功能尚未完全阐明。在本研究中，我们发现miR-32在HCC组织和细胞系中的表达上调，相反，磷酸酶和张力蛋白同源物（PTEN）的表达下降。此外，荧光素酶报告基因检测显示，miRNA-32通过与PTEN mRNA的3'-UTR结合而下调PTEN，并且miR-32的表达水平可通过PTEN/蛋白激酶B（Akt）信号通路影响肝癌细胞系的增殖、迁移和侵袭。PTEN的低表达可显著减弱敲低miR-32对肝癌细胞增殖、迁移和侵袭的抑制作用，提示miR-32可能是HCC治疗的一个潜在靶点。
