Human DYRK2 adenoviral particles

Colorectal cancer is one of the most common gastrointestinal tumors and is well-treated. However, if distant metastasis occurs, the treatment effect will be poor. Here, in vitro studies have shown that dual-specificity tyrosine-regulated kinase 2 (DYRK2) functions as a tumor suppressor in colorectal cancer by regulating cell survival, proliferation, and inducing apoptosis. In addition, DYRK2 expression was reduced in tumor tissues compared with non-tumor tissues of colorectal cancer, indicating a correlation with clinical prognosis. In this context, researchers designed a new therapeutic strategy to overexpress DYRK2 in tumors by adenovirus-mediated gene transfer. Studies have shown that adenovirus-mediated overexpression of DYRK2 in colon cancer cell lines can inhibit cell proliferation and induce apoptosis in vitro. In addition, forced expression of DYRK2 by direct or intravenous injection of adenovirus into tumors significantly inhibited tumor growth in mouse subcutaneous xenograft and liver metastasis models. Together, these results suggest that adenovirus-based DYRK2 overexpression can be a novel gene therapy approach for colorectal liver metastasis.

It has been reported that DYRK2 expression is reduced in CRC tissues. Furthermore, low expression levels of DYRK2 are associated with poor prognosis. Based on these findings, the researchers hypothesized that overexpression of DYRK2 by adenovirus (Ad-DYRK2) could serve as a novel therapeutic strategy for CRC. Since the expression levels of DYRK2 in HCT116 and RKO cell lines were lower than those in other cell lines, the researchers decided to focus on the effects of DYRK2 overexpression in HCT116 and RKO cells (Figure 1A). To evaluate the effects of DYRK2 on CRC cell proliferation and apoptosis, DYRK2 (Ad-DYRK2-WT), kinase-dead (K251R) DYRK2 mutant (Ad-DYRK2-KR), or Adv.empty as a control were transiently expressed (Figure 1B). Overexpression of DYRK2 suppressed the expression levels of c-Myc, Cyclin D1, and Cyclin D2, which are cell cycle progression markers (Figures 1B). The results of the cell proliferation assay (MTS assay) showed that overexpression of Ad-DYRK2-WT significantly suppressed tumor growth (Figure 1C). Similar effects were obtained in the colony formation assay (Figure 1D). Importantly, overexpression of a kinase-inactive construct (Ad-DYRK2-KR) partially counteracted the effect of Ad-DYRK2-WT (Figures 1B-D). In RKO cells, less significant differences were observed between Ad-DYRK2-WT and Ad-DYRK2-KR in the MTS assay. However, in the colony formation assay, the differences in both HCT116 and RKO cells were statistically significant (Figure 1D).

Figure 1. Forced expression of dual-specificity tyrosine-regulated kinase 2 (DYRK2) by adenovirus inhibits the growth of colon cancer cells in vitro. (Imaizumi Y, et al., 2022)