Role of LRRN4 in promoting malignant behavior in a p53-and Rb-defective human fallopian tube epithelial cell line

This study explored the role of leucine-rich repeat neuronal 4 (LRRN4) in ovarian carcinogenesis using the p53- and Rb-defective human fallopian tube epithelial cell line FE25. We evaluated the expression of LRRN4 in FE25 cells with and without LRRN4 knockdown by short hairpin RNA (shRNA) and studied its effects on cell proliferation, cell cycle, migration, invasion, chemotherapeutic sensitivity, apoptosis, and xenograft formation. The results showed that FE25 shRNA-LRRN4 cells exhibited more aggressive malignant behaviors than FE25 cells, including faster proliferation and increased cell distribution in the G2/M phase, Akt pathway activation, cell migration, and cell invasion, as well as decreased sensitivity to chemotherapeutic drugs. FE25 shRNA-LRRN4 cells exhibited reduced levels of apoptosis and decreased expression of cleaved caspase 3, 7, 8, and 9, indicating reduced apoptotic activity. Additionally, FE25 shRNA-LRRN4 cells showed decreased LRRN4 and CK7 expression and increased WT1 expression, suggesting a potential role for LRRN4 in ovarian carcinogenesis. FE25 shRNA-LRRN4 generated a xenograft in mice with increased levels of WT1 and TP53 expression compared to their levels in cells. Overall, this study suggests that LRRN4 may play a role in ovarian carcinogenesis by promoting aggressive malignant behavior in FE25 cells through the activation of the Akt pathway. These findings provide insights into the potential molecular mechanisms underlying ovarian cancer and may have implications for the development of new therapeutic targets for this disease.