Abstract 2793: LncRNA CRNDE facilitates head and neck cancer progression by modulating the tsmiRs-oncogenes network regulating multiple oncogenic signaling pathways

Abstract Recent studies have emphasized the pivotal role of long non-coding RNAs (lncRNAs) in tumorigenesis, with CRNDE identified as dysregulated in several cancers. This study explores the role of CRNDE in head and neck cancer (HNC), a globally prevalent malignancy. We demonstrate that CRNDE drives key malignant phenotypes in HNC, including enhanced cell migration, invasion, proliferation, and chemoresistance. RNA sequencing identified numerous downstream effectors, with 195 oncogenes significantly enriched in cancer-related pathways, such as focal adhesion, actin cytoskeleton organization, and PI3K-AKT, Ras, and Rap1 signaling. To elucidate the regulatory mechanisms of CRNDE, we observed that it predominantly localizes in the cytosol of HNC cells, suggesting its primary role in miRNA modulation. Bioinformatic analysis identified 14 miRNAs with strong regulatory potential. Among these, three tumor-suppressive miRNAs (TsmiRs)—miR-181c-5p, miR-29a-3p, and miR-29b-3p—were prioritized based on their clinical relevance from the TCGA-HNSC dataset. Further analysis revealed that these miRNAs potentially regulate 391, 417, and 137 target genes. Integrative analysis demonstrated that these hub miRNAs co-regulate 69 oncogenes, significantly influencing five cancer-related pathways. We constructed a comprehensive CRNDE-TsmiRs-Oncogenes regulatory network, uncovering a complex cross-regulatory mechanism. Moreover, we validated the CRNDE-miR-181c-PI3K/AKT3 axis as a critical pathway in HNC progression. Overexpression of miR-181c-5p markedly suppressed CRNDE-driven cancer progression by downregulating PI3K/AKT expression and mitigating malignant phenotypes, including migration, invasion, and chemoresistance. This study presents a novel CRNDE-TsmiRs-Oncogenes molecular network and highlights the CRNDE/miR-181c-5p/AKT axis as a promising biomarker and therapeutic target for improved HNC management. Citation Format: Ting Jui Lin, Ann Joy Cheng, Yin Ju Chen, Hung Hang Huang. LncRNA CRNDE facilitates head and neck cancer progression by modulating the tsmiRs-oncogenes network regulating multiple oncogenic signaling pathways [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 2793.