Abstract 3961: Identification of lncRNAs as potential novel therapeutic targets in triple negative breast cancer

Abstract Triple negative breast cancer (TNBC) lacks targeted therapies. Recently, our laboratory and other groups described long non-coding RNAs (lncRNAs) as new drivers of TNBC progression, which represent an exciting new avenue for targeted treatments. LncRNAs are the most versatile and diverse class of non-coding RNAs with roles in the progression of TNBC development, including cell proliferation, differentiation, apoptosis, metastasis and drug resistance. LncRNAs have greater tissue-specific expression compared to proteins and can be targeted using nucleotide sequence-specific RNA therapeutics, leading to reduced systemic toxicities when used as a cancer target. Using a combined approach of computational analysis of patient data and CRISPR functional screening, we identified hundreds of lncRNAs as novel drivers of TNBC. We prioritized one lncRNA target (lncTNBC3) with high translational potential. LncTNBC3 knockdown lead to reduced TNBC cell proliferation in two different loss-of-function models. To gain initial insights into the mechanism via which lncTNBC3 functions, RNA sequencing was carried out on knockdown cells, revealing that lncTNBC3 impacts cell cycle and DNA repair pathways. Cell cycle analysis confirmed an increase in G2/M cell cycle arrest upon lncTNBC3 knockdown. In conclusion, we have identified a promising novel lncRNA target with a role in TNBC growth. Citation Format: Megan O'Malley, Zohaib Rana, Debina Sarkar, Jolyn Chia, Sarah Diermeier. Identification of lncRNAs as potential novel therapeutic targets in triple negative breast 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 3961.