Abstract 5622: Uncovering the transcriptional regulation of TPPP3

Abstract

Abstract Tubulin Polymerization Promoting Protein 3 (TPPP3) is a protein coding gene primarily associated with microtubule bundling. However more recent research is beginning to reveal more diverse roles it may play in the cell, including B-catenin signaling and endothelial injury. TPPP3 has also been associated with increased cancer growth and proliferation as well epithelial to mesenchymal transition. However, it is unknown how TPPP3 is regulated. We used high grade serous ovarian cancer (HGSOC) as a model to uncover the regulation of TPPP3 as it is highly expressed in many HGSOC cases. To start, we downloaded ~500 HGSOC RNA-seq datasets from The Cancer Genome Atlas (TCGA) and, using python, created a co-expression network to identify a subset of genes exhibiting expression patterns correlated with TPPP3 across all datasets, resulting in the identification of 222 genes. Dynein arm assembly, cilia movement and assembly, and microtubule movement and structure were among the top GO-terms after gene ontology analysis. The genes associated with these processes are typically upregulated in the fallopian tube tissue which aligns with the fact that a majority of HGSOCs originate in the fallopian tube. Fork-head box J1 (FOXJ1) is a transcription factor associated with ciliogenesis and was among the top 222 genes from the co-expression network. It has not been confirmed to transcriptionally regulate TPPP3, but their expression patterns line up across many tissue types. In addition, the TPPP3 promoter contains an RFX2 binding site. RFX2 is DNA binding protein that FOXJ1 uses as a scaffold to bind to proximal promoters due to it binding at to DNA at a distal location. As a result of this evidence, we hypothesize that FOXJ1 transcriptionally regulates TPPP3 via RFX2. To test this hypothesis, we inhibited FOXJ1 and identified TPPP3 downregulation. We are further investigating the regulatory function of how TPPP3 is regulated. Citation Format: James W. Lord, Dmitry Leshchiner, Sachi Horibata. Uncovering the transcriptional regulation of TPPP3 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5622.