Significance of Musashi-1 expression in the Helicobacter pylori infected gastric mucosa and gastric cancer

在上一个财政年度，我们报道了神经RNA结合蛋白Musashi-1（MSI-1）诱导的胃粘膜由幽门螺杆菌感染和诱导CagA，幽门螺杆菌的毒力因子，此外，我们发现MSI-1在一些胃癌组织中过表达。在此，通过观察MSI-1过表达细胞的基因表达谱和表型的变化，研究MSI-1表达在胃癌中的意义。通过脂质体法将MSI-1基因转染到不表达MSI-1的AGS胃癌细胞中，建立了组成型表达MSI-1的AGS-Msi-1细胞。RT-PCR和Western blotting结果显示，与野生型和mock转染的细胞相比，BCL-2等抗凋亡分子在AGS-Msi-1细胞中的表达明显增强。此外，AGS-Msi-1-细胞形成了比野生型和模拟细胞显著更多的大尺寸集落。在软琼脂中。当通过血清剥夺诱导凋亡时，AGS-Msi-1细胞表现出抗凋亡特性，并且以显著更高的速率存活。此外，NF-κB活化在AGS-Msi-1细胞中被抑制。综上所述，本研究揭示MSI-1表达似乎通过表现出抗凋亡特性而有助于胃癌的发展。其抗凋亡作用可能与NF-κB通路的激活有关

In the last fiscal year, we reported that a neural RNA-binding protein Musashi-1 (MSI-1) was induced in the gastric mucosa by H.pylori infection and the induction was potently mediated by CagA, a virulent factor of H.pylori In addition, we found that MSI-1 was overexpressed in some gastric cancer tissue. Here, we investigated the significance of MSI-1 expression in gastric cancer by examining the changes in a gene expression profile and phenotypes in MSI-1-overexpressed cells.Transfecting the Msi-1 gene in AGS gastric cancer cells without MSI-1 expression by the lipofection method, we established AGS-Msi-1 cells that constitutively expressed MSI-1. RT-PCR and Western blotting revealed that anti-apoptotic molecules such as BCL-2 were remarkably induced in AGS-Msi-1 cells, compared with the wild type and mock-transfected cells. In addition, AGS-Msi-1-cells formed significantly more colonies large in size than the wild type and mock cells. in soft agar. When apoptosis was induced by serum deprivation, AGS-Msi-1 cells exhibited anti-apoptotic properties and survived at a significantly higher rate. Furthermore, NF-κB activation was suppressed in AGS-Msi-1 cells. Taken together, the present study revealed that MSI-1 expression seemed to contribute to the development of gastric cancer by exhibiting anti-apoptotic properties. The anti-apoptotic properties may be ascribed to the changes in the activation of the NF-κB pathways