SUZ12 promotes the malignant behavior of gastric cancer cells by CDKs.

Abstract

Zeste 12 Homolog (SUZ12), as a transcription factor, has been found to be highly expressed in a variety of tumors and promote tumor progression. We focus on revealing its role and mechanism in gastric cancer. Cellular level studies were conducted in mouse gastric cancer MFC cells by performing overexpression of SUZ12, overexpression of CDK6, and treatment with CDK6 inhibitor, respectively. Changes in cell viability, invasion, metastasis and colony formation were detected, and the expression variations of cell cycle regulatory proteins CDK6, P21, and Cyclin D were determined. During the animal experimentation, a mouse xenograft model was established. After transplantation of SUZ12-overexpressing MFC-SUZ12, the tumor growth was compared with that in MFC, and the tissue expressions of CDK-6, SUZ12, and Cyclin D were examined. Overexpression of SUZ12 could enhance the viability of MFC cells while upregulating their migration, invasion and colony formation abilities, which promoted the expression of CDK6, P21, and Cyclin D. CDK6 inhibitor, on the other hand, could suppress the effects of SUZ12 overexpression and weaken the cell viability and malignant behavior. Overexpression of CDK6 also promoted the MFC viability and malignant behavior. We found that SUZ12 exerted its effects by promoting the expression of downstream cyclin CDK6. At the animal level, the mice xenografted with SUZ12-overexpressing MFC cells exhibited larger tumor volumes, as well as elevated cyclin expression.SUZ12 promotes the proliferation and malignant behavior of gastric cancer cells by regulating the expression of downstream CDK6.