miR-372 regulates cell cycle and apoptosis of ags human gastric cancer cell line through direct regulation of LATS2
miR-372 regulates cell cycle and apoptosis of ags human gastric cancer cell line through direct regulation of LATS2
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DOI：
10.1007/s10059-009-0158-0
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发表时间：
2009-12-01
影响因子：
3.8
通讯作者：
Kim, Kye-Seong
中科院分区：
文献类型：
--
作者：
Cho, Wha Ja;Shin, Jeong Min;Kim, Kye-Seong
以前，我们已经报道了miR-372在人类胚胎干细胞中的组织特异性和阶段特异性表达，到目前为止，没有多少报道推测这种microRNA（miRNA）的功能。本研究筛选了包括胃癌细胞系在内的多种人类癌细胞系，首次发现miR-372仅在AGS人类胃腺癌细胞系中表达。反义miR-372寡核苷酸（AS-miR-372）抑制miR-372可抑制AGS细胞增殖，使细胞周期阻滞于G2/M期，并增加AGS细胞凋亡。此外，AS-miR-372处理增加了LATS 2的表达，而miR-372的过表达降低了由LATS 2 mRNA的3'非翻译区（3' UTR）驱动的荧光素酶报告基因活性。LATS 2的过表达在AGS细胞中诱导的变化与用AS-miR-372处理的AGS细胞中的变化相似。总之，这些发现证明了miR-372通过下调肿瘤抑制基因LATS 2在控制细胞生长、细胞周期和凋亡中的致癌作用。
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.