Abstract A065: The Role of miR-100 in lung cancer cell line: Relevance to cancer biology and potential therapy

Abstract

Lung cancer remains the leading cause of cancer-related mortality worldwide, with approximately 1.8 million deaths annually. Despite advances in diagnostics and targeted therapies, survival remains poor due to late-stage diagnosis, tumor heterogeneity, and therapeutic resistance. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression and play a key role in cancer biology. miR-100 has been reported as a tumor suppressor in several malignancies; however, its role and downstream regulatory network in lung cancer remain incompletely understood. This study aims to investigate the biological role of miR-100 in lung cancer and explore its therapeutic relevance. An integrative approach combining bioinformatics and experimental validation was used. Public datasets (TCGA, UALCAN, Linkedomics, and KM-Plotter) were analyzed to assess miR-100 expression, associated genes, and survival outcomes. Candidate genes were selected based on differential expression, prognostic relevance, and predicted interaction with miR-100. Functional validation was performed in A549 and BEAS-2B cell lines using qPCR following transfection with miR-100 mimics and inhibitors. Drug repurposing analysis was conducted using iLINCS. miR-100 was significantly downregulated in lung tumor tissues compared to normal tissues and was associated with improved overall survival (HR = 0.85, p = 0.033). ST6GALNAC4 was identified as a key gene associated with miR-100, showing differential expression, survival relevance, and predicted targeting. TXNDC11 was identified as a functionally related gene involved in oxidative stress pathways. In vitro validation confirmed reduced miR-100 expression in A549 cells compared to BEAS-2B cells. Modulation of miR-100 expression resulted in significant dysregulation of both ST6GALNAC4 and TXNDC11, supporting the computational findings. Drug signature analysis identified Vorinostat as a potential candidate capable of reversing the observed molecular profile. This study identifies a novel regulatory axis involving miR-100, ST6GALNAC4, and TXNDC11 in lung cancer. These findings highlight the role of miR-100 in glycosylation and oxidative stress pathways and support its potential as both a biomarker and therapeutic target. Additionally, Vorinostat emerges as a promising candidate for drug repurposing in this context. “Artificial intelligence (AI) tools were used solely to improve language clarity and readability. The scientific content, analysis, and conclusions are entirely the responsibility of the authors.” Basil Alotaibi, Arwa Alsubait. The Role of miR-100 in lung cancer cell line: Relevance to cancer biology and potential therapy [abstract]. In: Proceedings of AACR Drug Discovery and Development (AACR D3) Conference; 2026 Jul 21-24; Boston, MA. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(14_Suppl):Abstract nr A065.