Kinase DYRK2 Acts as a Regulator of Autophagy and an Indicator of Favorable Prognosis in Gastric Carcinoma

Abstract

Background: Gastric cancer (GC) is the third leading cancer-causing 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. Methods: The immunohistochemistry, statistical and bioinformatics analyses were used to detect the DYRK2 expression in stomach tissues. The role of DYRK2 in GC was analysed via nude mouse model, CCK8, wound healing and transwell assays. The Western blotting and immunofluorescent experiments were also performed to show the relationship between DYRK2 expression and epithelial-mesenchymal transition (EMT) / autophagy progress. Findings: 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. In vitro, the 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 found that DYRK2 inhibits the occurrence of EMT. The nude mouse model also indicated that DYRK2 does indeed inhibit tumor growth. Finally, we reported that DYRK2 promotes autophagy by Western blotting and immunofluorescent technology. Interpretation: DYRK2 may be a good reference indicator for the clinical diagnosis of GC. Funding Statement: This work was supported by the National Natural Science Foundation of China (81572390, 81874067); Jiangsu Provincial Science and Technology Department Social Development - Clinical Frontier Technology (BE2018673); the 13th Five Years Key Talent's Subsidy Project in Science and Education of Jiangsu Province (ZDRCA2016051). Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: The research method was approved by the Human Research Ethics Committee of the Affiliated Hospital of Nantong University, and the review number is 2018-K020. All studies involving animals were approved by the Nantong University Institutional Animal Care and Use Committee (No. 20150307-006).