Abstract P78: Identification of Novel Non-Coding RNAs and Phytochemicals for Targeting Different Cell Death Mechanisms in Triple-Negative Breast Cancer

Abstract Triple-Negative Breast Cancer (TNBC) is an aggressive and heterogeneous subtype of breast cancer characterized by the absence of estrogen, progesterone, and HER2 receptors, which limits the effectiveness of current targeted therapies. Emerging evidence highlights the crucial role of non-coding RNAs (ncRNAs), including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), in regulating gene expression and different cell death pathways such as apoptosis, ferroptosis etc. This study employs an integrative network pharmacology and structural biology approach to explore the interaction between ncRNAs, phytochemicals in different cell death mechanisms, aiming to identify novel therapeutic targets in TNBC. Key cell death-related targets were curated and linked to their corresponding mRNAs, miRNAs, and lncRNAs using databases such as miRTarBase, TargetScan, ENCORI, CTD, and Lnc2Cancer. Phytochemicals with known or predicted anticancer effects were screened for their regulatory interactions with these RNAs using SM2miR and CTD databases. Competing endogenous RNA (ceRNA) networks, protein–protein and RNA–molecule interactions were analyzed through STRING and STITCH, and hub genes were identified via CytoHubba. Further validation involved expression and survival analyses, functional enrichment, and mutational profiling. Notably, lncRNA NEAT1 and miR-let7bHG were identified as hub regulators within this network. NEAT1 exhibited consistent upregulation in TNBC and was significantly correlated with patient survival. Both RNAs participate in key oncogenic pathways related to apoptosis and cell proliferation. Additionally, PTEN, a well-known tumor suppressor frequently altered in TNBC, was identified as a significant mRNA target. Importantly, the small molecule Cyclosporine-A was validated by molecular docking on TP53 and EGFR. Overall, we identified a significant small molecule by a structural biology approach, suggesting its potential impact on the cell death pathways in TNBC. Citation Format: Reshmi Kumari, Satarupa Banerjee. Identification of Novel Non-Coding RNAs and Phytochemicals for Targeting Different Cell Death Mechanisms in Triple-Negative Breast Cancer [abstract]. In: Proceedings of Frontiers in Cancer Science 2025; 2025 Nov 5-7; Singapore. Philadelphia (PA): AACR; Cancer Res 2026;86(13_Suppl):Abstract nr P78.