Understanding the Role of Pyruvate Dehydrogenase Kinase 3 in Gynecological Cancers

Pyruvate dehydrogenase kinase 3 (PDK3) is a key regulatory enzyme of the pyruvate dehydrogenase complex that determines the fate of a cell towards oxidative phosphorylation or aerobic glycolysis through metabolic reprogramming. This study was designed to examine the role of PDK3 in gynecological cancers via in silico analysis and its conformation via in vitro experiments. Analysis of gynecological cancer datasets from the TCGA and CCLE databases suggested significant upregulation of PDK3 in breast, cervical, and endometrial cancer samples compared with the corresponding normal samples. KEGG pathway enrichment analysis revealed that pathways associated with cancers, viral carcinogenesis, and human papilloma virus infection were highly enriched. PDK3 upregulation affected the overall survival of breast and cervical cancer patients according to Kaplan–Meier survival analysis. PDK3 upregulation affected the proportion and distribution of immune cells in breast, cervical, and endometrial cancer. Furthermore, we experimentally showed that PDK3 knockdown inhibits the proliferation and growth of SiHa cells. Overall, we found that PDK3 may be an oncogene, and measuring its expression may be of prognostic and therapeutic significance in gynecological cancers.