CDK13-Mediated Cell Cycle Disorder Promotes Tumorigenesis of High HMGA2 Expression Gastric Cancer

The inhibitor of CDK4/6 has been clinically used for treating certain types of cancer which are characterized by G0/G1 acceleration induced by the CDK4/6-RB1 pathway. On the contrary, the cell cycle-related molecules are abnormal in over 50% of the patients with gastric cancer (GC), but the efficiency of inhibiting CDK4/6 does not work well as it is expected. In our study, we found HMGA2 promotes GC through accelerating the S-G2/M phase transition, instead of G0/G1. We also found CDK13 is the direct target gene of HMGA2. Importantly, we analyzed 200 pairs of GC and the adjacent tissue and proved the positive relation between HMGA2 and CDK13; moreover, high expression of both genes predicts a poorer prognosis than the expression of single gene does. We explored the effect of the novel CDK12/13 inhibiting agent, SR-4835, on high HMGA2 expression GC and found inhibition of both genes jointly could reach a satisfied result. Therefore, we suggest that inhibition of CDK13 and HMGA2 simultaneously could be an effective strategy for high HMGA2 expression GC. To detect the expression of both genes simultaneously and individually could be of benefit to predict prognosis for GC.

Automated summary

In this study, it was found that HMGA2 promotes gastric cancer growth by affecting the S-G2/M phase transition instead of G0/G1 acceleration, and CDK13 is a direct target gene of HMGA2 with a positive relationship between the two.