Overexpression of Pyruvate Kinase Type M2 (PKM2) Promotes Ovarian Cancer Cell Growth and Survival Via Regulation of Cell Cycle Progression Related with Upregulated CCND1 and Downregulated CDKN1A Expression
Bin Zheng, Fangfang Liu, Li Zeng, Li Geng, Xiaojuan Ouyang, Kai Wang, Qiaojia Huang
The School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian, China (mainland)
Med Sci Monit 2018; 24:3103-3112
Many findings have shown that pyruvate kinase type M2 (PKM2) plays crucial roles in regulating the occurrence and development of various human cancers; however, its roles in ovarian cancer oncogenesis remain to be determined.
MATERIAL AND METHODS: The expression intensity of PKM2 in ovarian cancer tissues was examined by immunohistochemistry (IHC), and was then correlated to patient clinicopathologic characteristics. The roles of PKM2 in ovarian cancer cell proliferation, growth, and survival were examined by CCK-8, colony forming, and flow cytometry assays. The potentially involved molecular were then investigated by Western blot analysis.
RESULTS: IHC results showed that PKM2 was overexpressed in 100 of 114 (87.7%) serous ovarian cancer tissues as compared with 50 cases of non-cancerous ovarian tissues, and was associated with tumor size ≥7.5 cm and <7.5 cm (p<0.05). Overexpression of PKM2 in SKOV3 and HEY ovarian cancer cells by transfection with PKM2 lentivirus vector led to increased cell proliferation, growth, and survival, which may be related with PKM2 being able to increase cell cycle progress: G1 stage decreased, whereas S stage significantly increased. In contrast, all functions of SKOV3 and HEY cells described above were reversed by knocked down PKM2 expression using siRNA. Further data showed that overexpressed PKM2 led to increased CCND1 and decreased CDKN1A expression, whereas underexpressed PKM2 led to decreased CCND1 and increased CDKN1A expression in ovarian cancer cells.
CONCLUSIONS: PKM2 may play important roles in ovarian cancer development and may be a treatment target for this cancer.
Keywords: Cell Proliferation, Cell Survival, Cyclin D1, Cyclin-Dependent Kinase Inhibitor p21, Pyruvate Kinase