Kinase DYRK2 acts as a regulator of autophagy and an indicator of favorable prognosis in gastric carcinoma
Kinase DYRK2 acts as a regulator of autophagy and an indicator of favorable prognosis in gastric carcinoma
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激酶 DYRK2 作为自噬的调节因子和胃癌良好预后的指标
DOI：
10.1016/j.colsurfb.2021.112182
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Jianfei Huang
中科院分区：
文献类型：
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作者：
Xiaojing Zhang;Runze Xiao;Bing Lu;Han Wu;Chunyi Jiang;Peng Li;Jianfei Huang
胃癌(GC)是全球第三大癌症相关死亡原因，因此需要新的、更具特异性的胃癌分子。在此，我们发现双特异性酪氨酸磷酸化调节蛋白2(DYRK2)可能是胃癌的特异性标志物。免疫组织化学(IHC)、统计学和生物信息学分析检测胃组织中DYRK2的表达。通过裸鼠模型和CCK-8、创面愈合和Transwell检测分析DYRK2在GC中的作用。Western blotting和免疫荧光实验也阐明了DYRK2的表达与上皮-间充质转化(EMT)和自噬进展的关系。我们发现DYRK2在胃癌组织中的表达低于良性或正常组织，高表达的患者预后良好。体外实验结果表明，DYRK2的表达抑制了GC的增殖、迁移和侵袭等致瘤活性。通过分析DYRK2表达改变后EMT标志物的表达，我们观察到DYRK2对EMT的发生有抑制作用。裸鼠模型显示DYRK2对肿瘤生长有抑制作用。最后，我们用Western blotting和免疫荧光分析发现DYRK2促进了自噬。根据这些数据，DYRK2可能是临床诊断GC的一个很好的参考指标。
Gastric cancer (GC) is the third leading cause of cancer-related death worldwide; therefore, new and more specific molecules for GC are needed. Here, we found that dual specificity tyrosine phosphorylation regulated kinase 2 (DYRK2) may be a specific marker for GC. Immunohistochemistry (IHC) and statistical and bioinformatics analyses were conducted to detect DYRK2 expression in stomach tissues. The role of DYRK2 in GC was analyzed with a nude mouse model and CCK-8, wound healing and Transwell assays. Western blotting and immunofluorescence experiments were also performed to elucidate the relationship between DYRK2 expression and both epithelial-mesenchymal transition (EMT) and autophagy progression. We found that DYRK2 expression in GC tissues was lower than that in benign or normal tissues, and patients with high DYRK2 expression had a good prognosis. The in vitro results showed that DYRK2 expression inhibited the tumorigenic activities of GC, including proliferation, migration, and invasion. By analyzing the expression of EMT markers after altering DYRK2 expression, we observed that DYRK2 inhibits the occurrence of EMT. The nude mouse model revealed that DYRK2 inhibits tumor growth. Finally, we used Western blotting and immunofluorescence assays and found that DYRK2 promotes autophagy. Based on these data, DYRK2 may be a good reference indicator for the clinical diagnosis of GC.