The homeobox (HOX) gene family plays a fundamental role in carcinogenesis. However, the oncogenic mechanism of HOXC10 in head and neck squamous cell carcinoma (HNSCC) remains unclear. In the present study, it was revealed that HOXC10 expression was significantly higher in HNSCC tissues than in adjacent tissues, and a high level of HOXC10 was closely associated with worse clinical outcomes. HOXC10 overexpression promoted HNSCC cell proliferation, migration, and invasion, both in vitro and in vivo. Mechanistically, chromatin immunoprecipitation sequencing revealed that HOXC10 drove the transcriptional activation of a disintegrin and metalloproteinase 17 (ADAM17), and the ADAM17/epidermal growth factor receptor (EGFR)/ERK1/2 signaling pathway facilitating the proliferation of HNSCC. Furthermore, mass spectrometric analysis indicated that HOXC10 interacted with ribosomal protein S15A (RPS15A) and enhanced RPS15A protein expression, activating the Wnt/β‑catenin pathway and contributing to invasion and metastasis of HNSCC. Additionally, the methylated RNA immune precipitation and RNA antisense purification assays showed that N⁶‑methyladenosine (m⁶A) writer, methyltransferase‑like 3, catalyzed m6A modification of the HOXC10 transcript, m6A reader insulin like growth factor 2 mRNA binding protein (IGF2BP)1 and IGF2BP3 involved in recognizing and stabilizing m⁶A‑tagged HOXC10 mRNA. In summary, the present study identified HOXC10 as a promising candidate oncogene in HNSCC. The m⁶A modification‑mediated HOXC10 promoted proliferation, migration, and invasion of HNSCC through co‑activation of ADAM17/EGFR and Wnt/β‑catenin signaling, providing a novel diagnostic and prognostic biomarker and a potential therapeutic target for HNSCC.

Nicotine, a crucial constituent of tobacco smoke, can bind to and activate nicotinic acetylcholine receptors (nAChRs), thereby regulating various biological functions. However, the specific mechanisms through which nicotine mediates nAChRs to regulate the metastasis of laryngeal squamous cell carcinoma (LSCC) remain elusive. In this study, smoking status was found to be closely associated with metastasis in patients with LSCC. In addition, nicotine exposure potentiated the hematogenous and lymphatic metastatic capacity of LSCC cells. Nicotine activates membrane-bound CHRNA5, promoting cell migration and invasion, EMT and cell–ECM adhesion in LSCC. Furthermore, this study demonstrated that the Ras superfamily protein RABL6 directly interacted with CHRNA5, which preferentially binds to the RABL6-39-279aa region, and this interaction was enhanced by nicotine. Nicotine-mediated activation of CHRNA5 enhanced its interaction with RABL6, triggering the JAK2/STAT3 signalling pathway and eventually augmenting the metastatic potential of LSCC cells. This study reveals a novel mechanism through which nicotine-mediated CHRNA5–RABL6 interaction promotes the metastasis of LSCC. The findings of this study may help to develop effective strategies for improving the outcome of patients with LSCC in clinical settings.

Smoking‐associated laryngeal squamous cell carcinoma (LSCC) is characterized by high metastatic potential and poor prognosis. However, the underlying molecular mechanisms remain insufficiently understood. This study utilized single‐cell RNA sequencing (scRNA‐seq) and spatial transcriptomics to explore the heterogeneity of the tumor microenvironment in smoking‐associated LSCC. Thirteen distinct cellular subpopulations within the tumor microenvironment are identified, with STC2 and ITGA5 emerging as smoking‐associated prognostic markers. STC2 exhibited bifurcated differentiation within tumor epithelial cells, categorized as Tumor_C1 and Tumor_C2. The two subtypes are linked to vascular permeability and DNA replication pathways, respectively. Mechanistically, nicotine activated the JAK2/STAT3 signaling pathway through CHRNA5, resulting in direct STAT3 binding to the STC2 promoter and modulation of its transcription. STC2 subsequently upregulated TGFBI, which interacted with ITGA5 on endothelial cells, regulating vascular permeability and facilitating hematogenous dissemination of LSCC cells. Furthermore, STC2 knockdown altered F‐actin cytoskeletal dynamics by modulating small GTPase signaling, impairing filopodia formation and epithelial polarity restoration. This study elucidates the tumor–endothelial interactions mediated by STC2 and ITGA5 in smoking‐associated LSCC, emphasizing their roles in tumor progression and vascular permeability. These findings suggest potential prognostic biomarkers and therapeutic targets to improve the clinical management of smoking‐associated LSCC.

MicroRNAs (miRNAs) are involved in carcinogenesis. However, the biological roles and underlying mechanism of miR-3690 in head and neck squamous cell carcinoma (HNSCC) progression are far from elucidated. In this study, we found that the expression level of miR-3690 in HNSCC tissues was significantly higher and correlated with poor clinical prognosis. HNSCC cells proliferation, migration, and invasion were promoted by miR-3690 overexpression, both in vitro and in vivo. Mechanistically, miRNA pulldown DNA-seq and luciferase reporter assays revealed that miR-3690 could directly activate CKS2 expression through targeting its promoter. Meanwhile, RNA pull down and mass spectrometry (MS) analysis suggested that upregulation of CKS2 by miR-3690 correlated with increased BPTF occupancy and H3K4me3 at CKS2 promoter. Additionally, luciferase reporter assays showed that miR-3690 facilitated Wnt/β-catenin signaling in HNSCC by repressing NKD1 expression through directly targeting its 3’-UTR. Finally, methylated RNA Immunoprecipitation (meRIP) and RNA pull down indicated that METTL3 and METTL14-mediated m6A modification accelerated pri-miR-3690 maturation through regulating the processing of pri-miR-3690 by DGCR8. In conclusion, miR-3690 may be a prognostic indicator and potential therapeutic target for HNSCC.

Background：The submental island flap (SIF) is valuable for head and neck reconstruction, but anatomical variations in submental vasculature pose surgical challenges. Systematic preoperative imaging may optimize planning and minimize vascular injury. Objective：To develop a standardized CT-based protocol for preoperative assessment of submental flap vasculature and characterize common anatomical patterns. Methods：Contrast-enhanced CT images from 109 patients (218 sides) were retrospectively analyzed between January and June 2024. A systematic protocol identified submental artery origin, traced its course relative to mylohyoid and digastric muscles, and determined facial vein drainage patterns using Fang's classification (Type I: internal jugular vein; Type II: external jugular vein; Type III: anterior jugular vein). Results：The submental artery origin was consistently identified within the "submental artery triangle" bounded by the mandible, mylohyoid muscle, and submandibular gland. The main trunk coursed deep to the digastric muscle in 31.1%, superficial in 33.0%, and penetrating through in 35.9%. Facial vein drainage patterns included Type I (56.3%), Type II (32.5%), and Type III (11.2%), with significant gender differences observed (p < 0.001). Conclusion： This standardized CT protocol enables reliable preoperative prediction of submental flap vascular anatomy, facilitating surgical planning and reducing risk of inadvertent vascular injury during flap harvest.