Abstract 3781: NF-κB classical and alternative signaling differentially regulate miRNA expression in ovarian cancer

Abstract

The NF-κB signaling pathway has been shown to contribute to epithelial ovarian cancer (EOC) through its classical and alternative pathways, characterized by the RelA and RelB transcription factors respectively. Previous studies have highlighted the role of RelA in sustaining the proliferative cancer cell population, while RelB aids in promoting the survival of chemoresistant, stem-like tumor-initiating cells (TICs) that promote disease relapse. In further characterizing the downstream effects of NF-κB signaling on EOC, we hypothesize NF-κB signaling differentially regulates the expression of several microRNAs (miRNAs) to promote TIC survival and proliferation through its classical and alternative pathways. miRNAs comprise a subset of small, noncoding RNAs that regulate gene expression, making them amenable for therapeutic targeting. Inducible shRNA stably expressed in OV90 EOC cells to knockdown RelA or RelB were analyzed by miR-seq to identify the differential expression of miRNAs in cells grown in TIC vs adherent (adh) conditions. Several miRNAs were differentially expressed in these conditions with RelA or RelB knockdown; we identified and validated the expression of two candidate miRNAs: hsa-miR-452-5p and hsa-miR-335-5p. We observed the decreased expression of hsa-miR-452-5p when either RelA or RelB is knocked down, while also observing the increased expression of hsa-miR-335-5p when RelA is knocked down. By inhibiting miR-452-5p in conjunction with disrupting NF-κB activity, we found changes in cell viability, sphere formation, and expression of the stem cell marker ALDH. Understanding the role of miRNA signaling in the context of NF-κB will better define the transcriptional roles of RelA and RelB in EOC. Ongoing work will further characterize the downstream targets of these miRNAs as potential therapeutic targets. Citation Format: Rahul D. Kamdar, Brittney S. Harrington, Soumya Korrapati, Emma Attar, Nathan Wong, Carrie D. House, Christina M. Annunziata. NF-κB classical and alternative signaling differentially regulate miRNA expression in ovarian cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3781.