Long non-coding RNA (lncRNA) CDKN2A-DT promotes proliferation, migration, and invasion of oral squamous cell...

CDKN2A-DT is a long non-coding RNA (lncRNA) located on chromosome 9 that plays a critical regulatory role in various malignancies, including ovarian cancer and lung cancer. However, its involvement in oral squamous cell carcinoma (OSCC) and the underlying molecular mechanisms remain poorly characterized. This study aims to investigate the expression profile, functional roles, and molecular mechanisms of lncRNA CDKN2A-DT in OSCC.

This study employs an integrative approach combining bioinformatics with both in vivo and in vitro investigations. The Cancer Genome Atlas (TCGA) database and a cohort of 23 paired clinical tissue samples (No. 2022079) were used to analyze the expression level of CDKN2A-DT and its associations with clinicopathological features and patient prognosis. Lentiviral vectors were employed to establish CDKN2A-DT knockdown and overexpression models in SAS and SCC-9 cell lines. Functional alterations were assessed through Cell Counting Kit-8 (CCK-8), colony formation, adhesion, Transwell migration/invasion, and wound healing assays. Protein expression levels of key components in the PI3K/AKT/mTOR signaling pathway were evaluated by Western blotting. In vivo tumorigenicity was examined using a nude mouse xenograft model (No. 202305001).

CDKN2A-DT expression was significantly upregulated in OSCC clinical tissue samples, correlating with gender, pathological grade, and tumor (T) stage. While node (N) stage and expression of CDKN2A-DT were identified as an independent prognostic factor for overall survival. Functional experiments demonstrated that CDKN2A-DT markedly enhanced the proliferative, adhesive, migratory, and invasive capacities of OSCC cells. Mechanistically, CDKN2A-DT activated the PI3K/AKT/mTOR signaling pathway by increasing the protein abundance of the PI3K regulatory subunit p85α, leading to elevated phosphorylation of AKT, mTOR, S6, Paxillin, and increased expression of matrix metalloproteinase-2 (MMP-2). In vivo studies confirmed that CDKN2A-DT overexpression significantly accelerated tumor growth in nude mice.

CDKN2A-DT promotes the malignant progression of OSCC through activation of the PI3K/AKT/mTOR signaling axis, which identifies it as a promising prognostic biomarker and supports its further investigation as a novel therapeutic target for OSCC.