Abstract 6785: MicroRNA-lincrna cross-talk in BRCA1-mutated breast cancer and its therapeutic implications

Abstract Breast cancer remains one of the leading causes of cancer-related mortality, characterized by its complexity and resistance to therapy. Triple-negative breast cancer (TNBC), a particularly aggressive subtype, lacks targeted therapies, making it challenging to treat. Long intergenic non-coding RNAs (lincRNAs) have emerged as critical regulators in cancer biology, with lincRNA-BC7 identified as a potential modulator of BRCA1. However, the exact mechanisms through which lincRNA-BC7 interacts with BRCA1. This study investigated the functional role of lincRNA-BC7 in regulating BRCA1 activity and its contribution to the biological response of TNBC cells to Olaparib. Using in breast cancer in vitro models. The cell biological response of TNBC cell line (MDA-MB-231) to Olaparib compared to the control group was evaluated. Gene expression analyses by RT-qPCR was done using LincRNA-BC-7 and BRCA1 specific primers. Furthermore, in silico bioinformatics analysis to map the molecular pathways involved was employed. This study revealed that miR-663a (has-miR-663a) could act as a sponge for lincRNA-BC7, thereby influencing its stability and expression levels. This interaction leads to alterations in the expression of target genes involved in key cancer hallmarks such as epithelial-mesenchymal transition (EMT), invasion, and metastasis. The competitive endogenous RNA (ceRNA) networks provide a framework for understanding how these non-coding RNAs interact at the post-transcriptional level, potentially affecting the progression of BRCA1-related breast cancer. Notably, both LincRNA-BC7 and BRCA1 gene expression levels were downregulated in Olaparib treated TNBC cells. Understanding the interplay between miR-663a and lincRNA-BC7and how this ceRNA network affects BRCA1 mutated TNBC may open avenues for novel therapeutic interventions. Citation Format: Olalekan Fadebi, Zodwa Dlamini, Rahaba Makgotso Marima. MicroRNA-lincrna cross-talk in BRCA1-mutated breast cancer and its therapeutic implications [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6785.