Abstract 5694: Elucidating areca nut-induced miRNA-mRNA regulatory networks in head and neck cancer pathogenesis

Abstract

Abstract Areca nut has been considered a high-risk carcinogen for head and neck cancer (HNC) in Southeast Asia, while its molecular effects, especially on the miRNA regulatory roles, remain elusive. This study characterized miRNA-mRNA networks associated with areca nut-related HNC. We integratively analyzed the areca nut-induced mRNA profile and TCGA-HNSC gene set. A total of 2575 genes were identified, with 1971 upregulated and 604 downregulated in cancers. The KEGG pathway analysis revealed that these genes were enriched in the cellular functions related to motility and stress response. Experimental studies confirmed that arecoline promoted cell migration, invasion, and chemo-radioresistance. We further cross-analyzed the miRNAs induced by areca nut and dysregulated in TCGA-HNSC data and defined 71 molecules affected, with 35 upregulation and 36 downregulation. Using the multimiR tool to map potential mRNA-miRNA interactions, we uncovered that these miRNAs were connected to 2173 genes. These molecules participated in several oncogenic mechanisms, such as ErbB and PI3K-Akt signaling, cell adhesion, and DNA damage response. We endeavored to establish miRNA-mRNA interaction networks with the functions of cellular motility and stress response via the Cytoscape analytical method. Our data revealed nexus comprising 41 miRNAs with 83 mRNAs, and 38 miRNAs with 66 mRNAs, respectively, co-regulate these two malignant functions. A key miRNA, miR-410-3p, downregulated in HNC and decreased following areca nut treatment, was studied. Ectopic expression of miR-410-3p attenuated areca nut-induced cell invasion and exerted modulatory effects on its target oncogenes, CRK. Thus, our study delineates a comprehensive view of the miRNA-mRNA interplay altered by areca nut, illustrating a sophisticated mechanism of carcinogenesis and suggesting new avenues for diagnostic and therapeutic strategies in HNC. Citation Format: Hung-Han Huang, Guo-Rung You, Kai-Hsin Lin, Yin-Ju Chen, Ann-Joy Cheng. Elucidating areca nut-induced miRNA-mRNA regulatory networks in head and neck cancer pathogenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5694.