Abstract 6678: Targeting long non-coding RNA LINC00324 using novel plant-derived exosome-like nanovesicles loaded with anticancer epigenetic modifiers effectively inhibits biomarkers of epithelial-mesenchymal transition in breast cancer

Abstract Despite recent advancements in the diagnostics and therapeutics of breast cancer, it continues to be the second leading cause of death among women worldwide. Therefore, identifying new potential biomarkers and molecular targets is essential for enhancing the diagnosis and treatment of BC patients. A wealth of evidence underscores the significant role of long non-coding RNAs in various biological processes, including tumorigenesis, which might offer new biomarkers and molecular targets for improved cancer detection and treatment. In this context, long intergenic non-coding RNA 00324 (LINC00324) has been associated with advanced cancer stage, larger tumor size, lymph node metastasis, and poorer prognosis across several cancer types. However, its biological function and molecular mechanisms in breast cancer remain largely unexplored. This study adopts an innovative approach aimed at challenging existing knowledge and research methodologies, with the goal of making significant advancements in breast cancer research. By exploring the role of LINC00324 as an oncogene in tumorigenesis and progression, the study may uncover crucial downstream oncogenic signaling pathways related to Epithelial-Mesenchymal Transition (EMT), which are linked to the hallmark features of breast cancer pathogenesis. This research could ultimately lead to the identification of a new biomarker for the diagnosis and prognosis of breast cancer, thereby transforming our understanding and treatment of the disease. In this study, we employed an innovative approach to downregulate the expression of LINC00324 across various breast cancer cell lines, ranging from well-differentiated to poorly differentiated types. This was accomplished using isolated novel plant-derived exosome-like nanovesicles (PELNVs), demonstrating specific biological effects, including anti-inflammatory and anti-tumor properties, while exhibiting minimal toxic side effects. PELNVs were a novel vehicle for delivering anticancer epigenetic modifier drugs and specific siRNA targeting LINC00324. Additionally, we investigated several downstream target biomarkers of epithelial-mesenchymal transition, including oncogenic targets such as Notch1, Notch4, Nanog, s6 kinase, β-catenin, and Stat3, both in vitro and in vivo. These findings suggest that LINC00324 could serve as a novel biomarker for diagnosis and prognosis. Outcome: Identifying the molecular classification of breast cancer subtypes based on the expression of individual biomarkers, such as LINC00324, might lead to the development of novel therapeutic biomarkers/targets for early detection, drug resistance, and personalized cancer treatments. Using PELNVs for drug delivery may inspire future research on plant-derived nanovesicles. Citation Format: Alaa Ashraf Al_Aaser, Nourhan El-Sayed El-Feel, Ahmed Samir Sultan. Targeting long non-coding RNA LINC00324 using novel plant-derived exosome-like nanovesicles loaded with anticancer epigenetic modifiers effectively inhibits biomarkers of epithelial-mesenchymal transition in breast cancer [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 6678.