A pan-cancer analysis of the oncogenic role of dual-specificity tyrosine (Y)-phosphorylation- regulated kinase 2 (DYRK2) in human tumors

Abstract

Although there have been studies correlating DYRK2 with a number of human cancers, there has been no pan-cancer analysis. Therefore, through the TCGA database, we conducted a related study on the expression of DYRK2 in cancers.The expression of DYRK2 is obviously increased in some cancers, while the opposite is true in others, and there is a clear association between its expression and the prognosis of cancer patients.The mutation of DYRK2 is also significantly correlated with patients’ prognosis in certain human tumors. In addition, phosphorylation and methylation levels of DYRK2 are different between tumor tissues and adjacent normal tissues in various tumors. In the tumour microenvironment, the expression of DYRK2 correlates with cancer-associated fibroblast infiltration, such as BLCA or HNSC. In order to fully understand the role of DYRK2 in different tumors, we conducted a pan-cancer analysis.

Discovery of Potent DYRK2 Inhibitors with High Selectivity, Great Solubility, and Excellent Safety Properties for the Treatment of Prostate Cancer

“…Dual-specificity tyrosine phosphorylation-regulated kinases (DYRKs) belong to the CMGC family and can be divided into class I (DYRK1A and DYRK1B) and class II (DYRK2, DYRK3, and DYRK4) groups. , DYRK2, the most studied class II DYRK, was found to play important roles in the regulation of cell proliferation, apoptosis, and migration. − Meanwhile, DYRK2 was identified as a target for PCa, and downregulation of DYRK2 prominently inhibited PCa. , However, few studies about DYRK2 inhibitors were reported, and most of the reported DYRK2 inhibitors are natural products or derivatives (Figure ). − Therefore, we focused on the development of novel DYRK2 inhibitors for the treatment of PCa.…”

“…7−9 Meanwhile, DYRK2 was identified as a target for PCa, and downregulation of DYRK2 prominently inhibited PCa. 10,11 However, few studies about DYRK2 inhibitors were reported, and most of the reported DYRK2 inhibitors are natural products or derivatives (Figure 1). 12−14 Therefore, we focused on the development of novel DYRK2 inhibitors for the treatment of PCa.…”

Discovery of the First Potent DYRK2 Proteolysis Targeting Chimera Degraders

“…DYRK2 has also been reported as a potential target for prostate cancer (PCa). Knockdown of DYRK2 in PCa cells suppressed cell proliferation and metastasis, promoted apoptosis, and caused a G1 arrest of the cell cycle. , Thus, DYRK2 is believed to be a promising target for cancer drug discovery.…”

“…As mentioned before, DYRK2 plays a significant and complex role in cancer cell growth and proliferation. − Cytotoxicity assays of CP134 and warheads were performed in the MM231 cell line (Figure S2f). The results showed that CP134 and A1 – A3 effectively inhibited cell proliferation with IC 50 values of 9.1, 5.6, 1.6, and 4.2 μM respectively, while curcumin (IC 50 > 20 μM) did not have an obvious effect on cell proliferation.…”

Hypomethylation of DYRK4 in peripheral blood is associated with increased lung cancer risk

“…The methylation levels of DYRK2 were higher in breast cancer and prostate adenocarcinoma, while lower in many other cancer types compared to corresponding tissues. 30 The hypermethylation of DYRK2 promoter region had been reported to be correlated with its downregulation in colorectal cancer tissues and the DNA methyltransferase inhibitor could induce DYRK2 expression and supppress proliferation in CRC cell lines. 31 The hypomethylation of DYRK2 resulted in 7-10 months reduction in the median survival time of the overall survival of ovarian cancer.…”