Molecular docking and dynamics reveal CCNB2 as a functional target of lncRNA ADAMTS9-AS1-002 in HNSCC

Head and neck squamous cell carcinoma (HNSCC) is a multifaceted disease, predominantly exaggerated by human papillomavirus infection due to critical cell cycle dysregulation, which further intricate tumor pathology. The present study investigated the oncogenic interaction potential of a novel long non-coding RNA (lncRNA) ADAMTS9-AS1-002 (ENST00000470447.1) with the G2/M checkpoint regulator Cyclin B2 (CCNB2) in HPV-positive HNSCC cases. Through integrative bioinformatics analyses, 420 differentially expressed genes (DEGs) overlapping with predicted ADAMTS9-AS1-002 targets were identified in the GEO dataset GSE250305. GO and KEGG enrichment analyses highlighted the significant roles of these genes in RNA processing (spliceosome formation) and cell cycle regulation. Among these, CCNB2 was markedly upregulated in HPV-positive samples and functionally implicated in tumor progression. Protein-RNA docking using HDOCK and HADDOCK demonstrated a stable interaction between ADAMTS9-AS1-002 and CCNB2, which was further validated by molecular dynamics simulations over 0-1000 ps (1 ns; Time axis in ps) showed a gradual increase in protein radius of gyration from 2.64 nm to 2.81 nm (mean 2.74 ± 0.07 nm), which is compatible with a compact complex but, given the short trajectory, should be considered preliminary support for feasibility rather than definitive stability. The interaction was localized to multiple lysine-rich regions of CCNB2, notably involving the key residues predicted by Pprint. These findings indicate a strong interaction between lncRNA ADAMTS9-AS1-002 and CCNB2 expression or function, with a substantial contribution to uncontrolled cell proliferation and oncogenic progression in HPV-positive HNSCC. Furthermore, this study also identifies CCNB2 as a critical downstream effector of ADAMTS9-AS1-002, which can be harnessed as a promising molecular signature for therapeutic intervention in head and neck cancers positive for HPV.