Abstract P115: Modulation Of Long Non-Coding RNAs In Triple-Negative Breast Cancer Cells By Tocotrienol-rich Fraction from Palm Oil

Abstract Breast cancer is the leading cause of cancer-related mortality among women worldwide. Triple-negative breast cancer (TNBC), representing ∼15% of cases, disproportionately contributes to this burden due to its aggressive growth, absence of targeted therapies, and high rates of chemoresistance. Tocotrienol-rich fraction (TRF), a vitamin E mixture with documented cytotoxic effects in preclinical models, represents a promising therapeutic candidate for TNBC. However, its mechanisms of action—especially the involvement of long non-coding RNAs (lncRNAs), key mediators of tumour progression and drug response—remain poorly understood. This study investigated the role of lncRNAs in mediating the cytotoxic effects of TRF in TNBC. MDA-MB-468 cells were treated with TRF (17 µg/ml, 72 hours), and transcriptomic profiling was performed using the Clariom™D microarray. Differentially expressed genes were identified (|fold change| > 2, p < 0.05) and then used to construct a lncRNA-mRNA co-expression network (Pearson’s correlation, |r| > 0.99, p < 0.05). Pathway enrichment analysis of the co-expressed mRNAs was carried out using the clusterProfiler package and the Reactome database. The network was visualised with Cytoscape and the hub genes were identified via cytoHubba with the Maximal Clique Centrality algorithm. TRF treatment altered the expression of 2,481 genes, including 306 lncRNAs (200 upregulated, 106 downregulated). The top enriched pathways identified by the functional enrichment of co-expressed mRNAs were related to the cell cycle and endoplasmic reticulum stress (ERS) pathways. Notably, DLGAP1-AS2 was identified as a highly upregulated hub gene and was correlated with the increased expression of PERK and CHOP, two key effectors of the unfolded protein response, an ERS pathway, which is capable of triggering apoptosis. These findings identify lncRNAs as important mediators of TRF-induced cytotoxicity in TNBC, and implicate DLGAP1-AS2 as a potential regulator of ERS–mediated apoptosis via the PERK/CHOP axis. Citation Format: Jacelyn Lee Sweet Yee, Uma Devi Palanisamy, Kasthuri bai Magalingam, Reyhaneh Farghadani, Ammu Kutty Radhakrishnan. Modulation Of Long Non-Coding RNAs In Triple-Negative Breast Cancer Cells By Tocotrienol-rich Fraction from Palm Oil [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 P115.