BioCentury
ARTICLE | Distillery Therapeutics

Cancer

April 10, 2018 10:56 PM UTC

Patient sample and mouse studies suggest inhibiting PRKCI’s circular RNA (circRNA) could help treat lung adenocarcinoma. In patient samples, levels of PRKCI circRNA -- which is derived from exons 15 and 16 -- were higher in tumors than in matched adjacent normal lung tissue, and the high tumor levels of PRKCI circRNA were associated with large tumor size, advanced tumor stage and poor overall survival. In two human lung adenocarcinoma cell lines, siRNA targeting PRKCI circRNA decreased proliferation and migration compared with a non-targeting siRNA. In another human lung adenocarcinoma cell line, the siRNA targeting PRKCI circRNA plus Iressa gefitinib decreased proliferation compared with either agent alone. In a xenograft mouse model of lung adenocarcinoma, tumor-specific knockdown of PRKCI circRNA decreased tumor growth compared with normal PRKCI circRNA expression. In a patient-derived xenograft (PDX) mouse model of lung adenocarcinoma, intratumoral injection of a cholesterol-conjugated siRNA targeting PRKCI circRNA decreased tumor growth compared with cholesterol-conjugated non-targeting siRNA. Next steps could include identifying and testing PRKCI circRNA inhibitors in the models...

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