Liu Ning, Jiang Fan, Ye Mulin, Wang Bangjie, Ge Dongsheng, Chang Shunwu
Department of Gastrointestinal Surgery, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou 570311, Hainan Province, China.
Center of Gerontology, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou 570311, Hainan Province, China.
Cytokine. 2022 May;153:155830. doi: 10.1016/j.cyto.2022.155830. Epub 2022 Mar 2.
Human gastric cancer is a leading cause of cancer mortality in the world wide. We found that the expression of IL-17a was significantly increased in gastric cancer cells. Treatment with recombinant IL-17a (rIL-17a) can increase migration, invasion and epithelial to mesenchymal transition (EMT) of gastric cancer cells. Further, Snail, a key factor to regulate EMT, was significantly increased in rIL-17a-treated gastric cancer cells. While knockdown of Snail can abolish IL-17a-induced EMT of gastric cancer cells. Mechanistically, IL-17a can promote the translation efficiency of Snail, while had no effect on its mRNA expression or protein stability. Further, we found that IL-17a can increase the expression of HuR, which markedly promoted translation of Snail mRNA. While knockdown of HuR can reverse rIL-17a-induced expression of Snail and EMT of gastric cancer cells. Collectively, our data suggested that HuR confers IL-17a induced migration and invasion of gastric cancer cells via upregulation of Snail translation.
人类胃癌是全球癌症死亡的主要原因。我们发现白细胞介素-17a（IL-17a）在胃癌细胞中的表达显著增加。用重组IL-17a（rIL-17a）处理可增加胃癌细胞的迁移、侵袭及上皮-间质转化（EMT）。此外，作为调节EMT的关键因子，Snail在rIL-17a处理的胃癌细胞中显著增加。而敲低Snail可消除IL-17a诱导的胃癌细胞EMT。机制上，IL-17a可促进Snail的翻译效率，而对其mRNA表达或蛋白质稳定性无影响。此外，我们发现IL-17a可增加HuR的表达，这显著促进了Snail mRNA的翻译。而敲低HuR可逆转rIL-17a诱导的Snail表达及胃癌细胞的EMT。总体而言，我们的数据表明，HuR通过上调Snail翻译赋予IL-17a诱导的胃癌细胞迁移和侵袭能力。
