miR-203通过CD82/KAI1表达抑制人肺癌细胞中卷曲蛋白2的表达。
miR-203 Inhibits Frizzled-2 Expression via CD82/KAI1 Expression in Human Lung Carcinoma Cells.
作者信息
Mine Mariko, Yamaguchi Kojiro, Sugiura Tsuyoshi, Chigita Satomi, Yoshihama Naoya, Yoshihama Rumi, Hiyake Naomi, Kobayashi Yosuke, Mori Yoshihide
机构信息
Division of Maxillofacial Diagnostic and Surgical Sciences, Department of Oral and Maxillofacial Surgery, Graduate School of Dental Science, Kyushu University Maidashi, Higashi-ku, Fukuoka, Japan.
Department of Maxillofacial Diagnostic and Surgical Science, Field of Oral and Maxillofacial Rehabilitation, Graduate School of Dental Science, Kagoshima University Sakuragaoka, Kagoshima, Japan.
出版信息
PLoS One. 2015 Jul 1;10(7):e0131350. doi: 10.1371/journal.pone.0131350. eCollection 2015.
CD82/KAI1, a member of the tetraspanin superfamily, is a suppressor of metastasis and CD82 inhibits canonical Wnt signaling via downregulation of several Frizzled (FZD) isoforms, resulting in accumulation of β-catenin at the cell membrane. In this study, we investigated the mechanism through which CD82 inhibited FZD expression by examining the effects of microRNAs (miRNAs). The miRanda algorithm predicted 11 miRNAs from FZD sequences. Among these miRNAs, CD82 caused upregulation of miR-203 (by 2.095-fold) and downregulation of miR-338-3p (by 0.354-fold) as compared with control cells. Transfection with miR-203 and miR338-3p mimics or inhibitors revealed that miR-203 downregulated FZD2 mRNA (by 0.268-fold) and protein expression (by 0.701-fold). Moreover, transfection with the miR-203 mimic also inhibited cell migration. Therefore, these findings suggested that CD82 enhanced the expression of miR-203 and directly downregulate FZD2 expression, suppressing cancer metastasis by inhibition of the Wnt signaling pathway.
CD82/KAI1是四跨膜蛋白超家族的成员，是一种转移抑制因子，CD82通过下调几种卷曲蛋白（FZD）亚型来抑制经典Wnt信号通路，导致β-连环蛋白在细胞膜上积累。在本研究中，我们通过研究微小RNA（miRNA）的作用，探讨了CD82抑制FZD表达的机制。miRanda算法从FZD序列中预测出11种miRNA。在这些miRNA中，与对照细胞相比，CD82导致miR-203上调（2.095倍），miR-338-3p下调（0.354倍）。用miR-203和miR338-3p模拟物或抑制剂转染显示，miR-203下调FZD2 mRNA（0.268倍）和蛋白表达（0.701倍）。此外，用miR-203模拟物转染也抑制了细胞迁移。因此，这些发现表明，CD82增强了miR-203的表达并直接下调FZD2表达，通过抑制Wnt信号通路抑制癌症转移。
Zotero 插件