PKC iota Is a Promising Prognosis Biomarker and Therapeutic Target for Pancreatic Cancer

Background: As the highest prevalent pancreatic cancer, pancreatic ductal adenocarcinoma (PDAC) ranks the 7th lethal malignancy worldwide. The late diagnosis, chemotherapeutic resistance, and high associated mortality make PDAC a dilemma facing the oncologists. Protein kinase C (PKC) enzymes have been shown to be important in different cancer progression. Methods: To understand the pattern of PKC enzymes in PDAC, we examined all PKC family member genes expression in PDAC and matched normal tissues. The critical role of PKC iota was further investigated in different PDAC cells using cellular and molecular technology. Results: We found that PRKCI (PKC iota) was the most significantly overexpressed PKCs in pancreatic cancer. However, little is known about its role and regulation of oncogenic signaling pathways in pancreatic cancer. In this study, we confirmed the overexpression of PKC iota in PDAC, and this high expression was associated with poor prognosis of patients. We proved that knockdown of PKC iota by small interfering RNA or shRNA significantly inhibited pancreatic cancer cell growth and migration or invasion. Conversely, PKC iota overexpression promoted pancreatic cancer cell growth and migration. Moreover, bioinformatical and technical studies informed the participation of PKC iota in regression of apoptosis in PDAC cells, which may be related to the regulation of both PI3K/AKT and Wnt/beta-catenin pathways. Conclusions: Therefore, our results are adding more insight into the importance of PKC iota in pancreatic cancer. PKC iota induces pancreatic cancer progression through activation of PI3K/AKT and Wnt/beta-catenin signaling pathways, which may provide a promising therapeutic target for pancreatic cancer. (c) 2022 S. Karger AG, Basel