Addiction to protein kinase Cɩ due to PRKCI gene amplification can be exploited for an aptamer-based targeted therapy in ovarian cancer

• DOI: 10.1038/s41392-020-0197-8
• Publication Date: 2020-08-20T23:05:31Z
• Authors: Hina Rehmani; Yue Li; Tao Li; Ravi Padia; Ozlem Calbay; Lingtao Jin; Huijun Chen; Shuang Huang
• Keywords: Aptamer

PRKCI, the gene for protein kinase Cι (PKCι), is frequently amplified in ovarian cancer and recent studies have shown that PKCι participates ovary tumorigenesis. However, it unknown whether differentially involved growth/survival between PRKCI-amplified non-amplified cells. In this study, we analyzed patient dataset revealed PRKCI only PKC family member significantly amplification associated with higher expression. Using a panel of cell lines, found abundance generally amplification. Interestingly, silencing led to apoptosis cells but not those without amplification, thus indicating an oncogenic addiction PKCɩ Since small-molecule inhibitors characterized selectively block atypical PKCs did offer selectivity nor sensitivity were even cytotoxic non-cancerous surface or fallopian tube epithelial cells, designed EpCAM aptamer-PKCι siRNA chimera (EpCAM-siPKCι aptamer). EpCAM-siPKCι aptamer effectively induced also greatly deterred intraperitoneal tumor development xenograft mouse model. This study has demonstrated precision medicine-based strategy target subset contains aptamer-delivered may be used suppress such tumors.