Abstract A012: Identification of FOXJ1 as a novel regulator of TPPP3

Ovarian cancer is one of the deadliest gynecological malignancies and the sixth leading cause of cancer-related deaths among women. Chemoresistance represents one of the greatest hurdles in treatment, with the standard treatment of a platinum agent (cisplatin or carboplatin) and paclitaxel. This treatment plan is initially effective; however, approximately 80% of patients eventually develop platinum resistance and experience relapses. Previous work in our lab identified that tubulin polymerization promoting protein 3 (TPPP3) was highly expressed in cisplatin-resistant cell lines, but not in cisplatin-sensitive or -resensitized cells. TPPP3 is microtubule associated protein that is involved in microtubule bundling. It has also been implicated in tumor growth and metastasis multiple other cancers. In this study, we identified that Forkhead Box J1 (FOXJ1) is also elevated in cisplatin-resistant ovarian cancer. FOXJ1 shared a similar expression pattern to TPPP3, being elevated only in resistant cells and not in sensitive or resensitized ones. Using RNA-seq datasets from The Cancer Genome Atlas (TCGA), we constructed a coexpression network to identify genes whose expression correlates with TPPP3. In addition to FOXJ1, gene ontology analysis of the top hits showed enrichment in pathways related to cilia formation and structure. Given that FOXJ1 is a master regulator of motile cilia development and microtubules are essential structural components of cilia, we hypothesized that FOXJ1 regulates TPPP3 expression in ovarian cancer, contributing to chemoresistance. To test this hypothesis, we knocked down (KD) FOXJ1 to evaluate its effect on TPPP3 expression. After FOXJ1 KD, TPPP3 expression significantly decreased in multiple cisplatin-resistant cell lines. Further research is needed to fully characterize the regulatory mechanism of FOXJ1 and its effects on cisplatin resistance. Citation Format: James Lord, Sachi Horibata. Identification of FOXJ1 as a novel regulator of TPPP3 [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Ovarian Cancer Research; 2025 Sep 19-21; Denver, CO. Philadelphia (PA): AACR; Cancer Res 2025;85(18_Suppl):Abstract nr A012.