Biomedical Research Center, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan 682-060, Korea.
Mol Cells. 2009 Dec 31;28(6):521-7. doi: 10.1007/s10059-009-0158-0. Epub 2009 Nov 19.
Previously, we have reported tissue- and stage-specific expression of miR-372 in human embryonic stem cells and so far, not many reports speculate the function of this microRNA (miRNA). In this study, we screened various human cancer cell lines including gastric cancer cell lines and found first time that miR-372 is expressed only in AGS human gastric adenocarcinoma cell line. Inhibition of miR-372 using antisense miR-372 oligonucleotide (AS-miR-372) suppressed proliferation, arrested the cell cycle at G2/M phase, and increased apoptosis of AGS cells. Furthermore, AS-miR-372 treatment increased expression of LATS2, while over-expression of miR-372 decreased luciferase reporter activity driven by the 3' untranslated region (3' UTR) of LATS2 mRNA. Over-expression of LATS2 induced changes in AGS cells similar to those in AGS cells treated with AS-miR-372. Taken together, these findings demonstrate an oncogenic role for miR-372 in controlling cell growth, cell cycle, and apoptosis through down-regulation of a tumor suppressor gene, LATS2.
先前,我们已经报道了 miR-372 在人胚胎干细胞中的组织和阶段特异性表达,到目前为止,还没有多少报道推测这种 microRNA(miRNA)的功能。在这项研究中,我们筛选了各种人类癌细胞系,包括胃癌细胞系,首次发现 miR-372 仅在 AGS 人胃腺癌细胞系中表达。使用反义 miR-372 寡核苷酸(AS-miR-372)抑制 miR-372 的表达抑制了 AGS 细胞的增殖,将细胞周期阻滞在 G2/M 期,并增加了细胞凋亡。此外,AS-miR-372 处理增加了 LATS2 的表达,而 miR-372 的过表达降低了 LATS2 mRNA 3'非翻译区(3'UTR)驱动的荧光素酶报告基因活性。LATS2 的过表达诱导 AGS 细胞发生变化,类似于用 AS-miR-372 处理的 AGS 细胞。综上所述,这些发现表明 miR-372 通过下调肿瘤抑制基因 LATS2 在控制细胞生长、细胞周期和细胞凋亡方面发挥致癌作用。