This study investigated the expression profiles of the HMGA1 and HAND1 genes in laryngeal squamous cell carcinoma (LSCC) as well as in adjacent normal laryngeal mucosal tissues through the application of immunohistochemistry and RT-PCR methodologies. The objective was to investigate their possible roles in the initiation, advancement, invasion, and metastasis of LSCC. Both HMGA1 and HAND1 were detected in cancerous and adjacent normal tissues. Nevertheless, HMGA1 demonstrated a significantly elevated expression in LSCC tissues, while HAND1 displayed considerably reduced expression levels. Elevated HMGA1 expression was positively associated with lymph node metastasis (100.0% vs. 50.0%) and advanced clinical stage (91.7% vs. 44.4%), but was not associated with tumor histological grade, clinical type, or patient age. In contrast, reduced HAND1 protein expression was associated with lymph node metastasis, clinical stage, and pathological grade, suggesting a role in tumor progression and metastasis. Furthermore, a linear negative correlation was noted between the expressions of HMGA1 and HAND1, suggesting a potential regulatory interaction in which HMGA1 may suppress HAND1 expression. These results imply that HMGA1 and HAND1 have complementary functions in the pathogenesis of LSCC, with HMGA1 potentially facilitating tumor development and HAND1 serving as a suppressor. The interaction between these two genes may offer new perspectives on the molecular mechanisms that drive LSCC progression and metastasis.

Laryngeal cancer is a relatively uncommon malignancy with predisposing genetic factors that remain unclear. Single-nucleotide polymorphisms (SNPs) in genes involved in innate immune signaling may contribute to the development and progression of laryngeal carcinoma. This study aimed to evaluate the association of TLR4 (rs7037225, rs11536889, rs7037117) and MYD88 (rs7744, rs6853) polymorphisms with the risk of laryngeal squamous cell carcinoma (LSCC), as well as its clinical and pathological characteristics and survival. A retrospective case–control study involving 172 LSCC patients and 220 healthy controls was conducted. Genotyping was performed using real-time PCR from venous blood samples. MYD88 rs7744 was significantly associated with tumor size and lymph node involvement. Survival analysis showed a significant association between rs7744 and recurrence-free survival (RFS), with the AG and GG genotypes linked to poorer outcomes. Conversely, carriers of the TLR4 rs7037225 CT genotype showed significantly improved RFS, with p ranging from 0.024 to 0.037 across models. Considering the significant roles of TLR4 and MYD88 in Toll-like receptor signaling, these findings may reflect the involvement of innate immune pathways in LSCC progression. In summary, MYD88 rs7744 was associated with clinicopathological features and RFS, while TLR4 rs7037225 appeared to have a potential protective effect on survival.

Laryngeal squamous cell carcinoma (LSCC) is one of the most common types of head and neck cancer, posing a significant threat to public health. The spindle and kinetochore-associated complex subunit 3 (SKA3), a microtubule-binding subcomplex of the outer kinetochore, participates in cancer progression. However, its role in the progression of LSCC remains unclear. This study aimed to investigate the regulatory effects of SKA3 on LSCC progression and its underlying mechanism. In this study, the expression levels of SKA3 and aldo-keto reductase family 1 member C1 (AKR1C1) mRNA were assessed by quantitative real-time PCR. Protein expression was evaluated using western blotting. Cell proliferation was analyzed using the cell counting kit-8 assay, while apoptosis was assessed by flow cytometry. Cell migration and invasion were measured via Transwell assays. The levels of Fe2+ and glutathione were analyzed with colorimetric assays, while reactive oxygen species (ROS) levels were determined by flow cytometry. Chromatin immunoprecipitation and dual-luciferase reporter assays were employed to explore the interaction between SOX9 and SKA3. The impact of SKA3 silencing and AKR1C1 overexpression on tumor formation was investigated using a xenograft mouse model. The results showed that SKA3 expression was elevated in LSCC tissues and cells when compared with corresponding normal tissues and human nasopharyngeal epithelial cells. Silencing SKA3 suppressed LSCC cell proliferation, migration, and invasion, while promoting apoptosis and ferroptosis. SKA3 upregulated AKR1C1, a key ferroptosis-related gene, in TU177 and AMC-HN-8 cells. Overexpression of AKR1C1 mitigated the effects of SKA3 silencing on the malignant phenotypes of these cells. SOX9 was identified as a transcriptional activator of SKA3 in TU177 and AMC-HN-8 cells, and AKR1C1 overexpression reversed the inhibitory effect of SKA3 silencing on tumor growth in vivo. Thus, SKA3 played a pivotal role in the progression of LSCC through the SOX9/SKA3/AKR1C1 axis, suggesting that targeting SKA3 might have significant clinical implications for the treatment of LSCC.

ABSTRACT Background Laryngeal squamous cell carcinoma (LSCC) is a common head and neck malignancy with poor prognosis. The role of MYBL2, an oncogenic transcription factor, in the glycolytic reprogramming of LSCC remains unclear. Methods We integrated RNA-sequencing with public databases (TCGA, GEO) and tissue microarrays to assess MYBL2 expression and its clinical significance. Transcriptional regulation was verified by ChIP-qPCR and luciferase reporter assays. Signaling pathways and metabolic profiles were examined using Western blotting and Seahorse analysis (ECAR/OCR). Biological functions were evaluated by in vitro functional assays and in vivo xenograft models in female BALB/c nude mice. Results MYBL2 was significantly overexpressed in LSCC tissues and correlated with poor prognosis. Mechanistically, MYBL2 directly activates GTSE1 transcription. This regulation stimulates PI3K/AKT signaling to upregulate key glycolytic proteins (PKM2, HK2, GLUT1, LDHA), thereby driving metabolic reprogramming characterized by elevated glycolysis (ECAR) and suppressed mitochondrial respiration (OCR). Functionally, MYBL2 overexpression enhanced the proliferation, migration, and invasion of LSCC cells in vitro and promoted tumor growth in vivo. Importantly, these oncogenic effects were effectively reversed by GTSE1 knockdown or PI3K inhibition with LY294002, validating the pathway's functional significance. Conclusion The MYBL2-GTSE1 axis promotes LSCC progression through PI3K/AKT-mediated metabolic reprogramming, representing a promising therapeutic target.

Smoking, alcohol consumption, and high-risk human papillomavirus (HPV) infection are recognized risk factors for laryngeal squamous cell carcinoma (LSCC); however, approximately 20%-30% of patients lack typical exposure histories. Furthermore, HPV-positive patients exhibit significant prognostic heterogeneity, suggesting the complexity of multifactorial synergistic carcinogenesis. Recent studies have indicated that the unique anatomy and microenvironment of the larynx may mediate synergistic interactions between pathogens such as Epstein-Barr virus (EBV) and HPV. This functional "two-hit" model drives metabolic reprogramming, disrupts immune responses, and promotes immune evasion, thereby potentially fueling the malignant progression of LSCC. However, coexistence patterns and dynamic interaction mechanisms remain unclear. This systematic review of field advances aims to elucidate potential synergistic mechanisms between HPV and EBV, providing theoretical foundations for pathogen-based multitarget diagnostics and clinical treatment strategies to advance the precision prevention and treatment of LSCC.

Laryngeal squamous cell carcinoma (LSCC) is a significant subtype of head and neck cancers, with tobacco and alcohol being primary risk factors. Many studies have shown that human endogenous retroviruses (HERVs), specifically HERV-K and HERV-H, have been implicated in the development and progression of various cancers, including head and neck cancers; nevertheless, there is a lack of research on the expression levels of HERV-K and HERV‐H in LSCC. In this research, the differential expression of HERV-K Rec, Env, Np9, and HERV-H pol transcripts was assessed in 144 laryngeal biopsy specimens (72 polyps and 72 LSCC samples) utilizing quantitative Real‐time PCR. The results showed a significant upregulation of HERV-K Env and HERV-H pol in the LSCC group compared to the polyp group (p < 0.001), suggesting their potential role in LSCC progression. The ROC curve analysis further supported the diagnostic significance of HERV-H pol and HERV-K Env transcripts in distinguishing LSCC from noncancerous polyps (HERV-H pol: AUC = 0.86; HERV-K Env: AUC = 0.76). Moreover, being over 50 years old and having an opium addiction were linked to increased expression levels of HERV-H Pol and HERV-K Env, suggesting a potential connection between these elements and laryngeal cancer (p < 0.001). These results highlight the possible utility of HERV-H pol and HERV-K Env as biomarkers for the diagnosis and prognosis of LSCC. Undoubtedly, additional research is imperative to establish the clinical efficacy of these biomarkers.

Despite evidence linking histone lactylation to tumorigenesis, its specific regulatory role in laryngeal squamous cell carcinoma (LSCC) is still not well defined. Histone H3K18 lactylation (H3K18la) levels in LSCC tissues were analyzed by immunohistochemistry (IHC) and western blot, showing significantly higher levels than non-tumor tissues. Treatment with the sodium oxamate (SO) effectively reduced H3K18la level, thereby suppressing LSCC cell proliferation and migration while inducing apoptosis. Mechanistically, H3K18la upregulated Runt-related transcription factor 2 (RUNX2) expression, which in turn activated the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway to promote aggressive LSCC phenotypes. Our findings demonstrate that H3K18la facilitates LSCC progression by enhancing malignant cellular behaviors, thereby offering potential therapeutic targets for LSCC intervention.

SERPINH1 promotes malignant progression of laryngeal squamous cell carcinoma via COL7A1-mediated Wnt/β-catenin signaling.

Ceritinib (LDK378) inhibits laryngeal squamous cell carcinoma progression via regulating ROS-induced mitochondrial apoptosis and inducing oxidative stress.

Mitochondrial apoptosis induced by MNAT1 in laryngeal squamous cell carcinoma cells reverses drug resistance.

Lactate-related genes signature as a novel prognostic landscape in laryngeal squamous cell carcinoma: insights from 156 machine learning algorithms and in vitro validation.

Laryngeal squamous cell carcinoma (LSCC) is a malignant tumor with limited treatment options and poor prognosis in advanced stages. Arsenic trioxide (ATO), a drug well-known for treating acute promyelocytic leukemia, has shown potential antitumor effects in several solid tumors. This study aimed to investigate the role of ATO on LSCC proliferation and its underlying molecular mechanisms. LSCC cell lines (TU212, TU686, and AMC-HN-8) were treated with varying concentrations of ATO, and cell proliferation was evaluated using CCK-8, colony formation, and EdU assays. miRNA-sequencing identified differentially expressed miRNAs after ATO treatment, and bioinformatics tools predicted hsa-miR-573 target genes. The interaction between hsa-miR-573 and dynactin-associated protein (DYNAP) was validated by dual-luciferase reporter assays. Additionally, a xenograft tumor model was established to examine the in vivo effects of ATO on tumor growth. ATO significantly inhibited LSCC cell proliferation in a dose- and time-dependent manner. miRNA-sequencing identified hsa-miR-573 as significantly upregulated following ATO treatment, and functional studies demonstrated that hsa-miR-573 suppresses LSCC cell proliferation by directly targeting DYNAP. Overexpression of DYNAP promoted LSCC cell proliferation, while DYNAP knockdown reversed this effect. In vivo, ATO treatment suppressed tumor growth in nude mice without significant nephrotoxicity or cardiotoxicity. Mechanistically, ATO reduced the expression of DYNAP and inhibited the PI3K/AKT signaling pathway. ATO inhibited LSCC progression by upregulating hsa-miR-573, which directly targets DYNAP to suppress cell proliferation and disrupt the PI3K/AKT signaling pathway. These findings supported the potential of ATO as a therapeutic agent for LSCC.Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-025-12881-z.

To elucidate the role of eukaryotic translation initiation factor 3 subunit B (EIF3B) in laryngeal squamous cell carcinoma (LSCC) progression and its regulatory mechanism. Integrated bioinformatics analysis (GEO, TCGA), immunohistochemistry (IHC), lentiviral-mediated gene knockdown/overexpression, co-immunoprecipitation (Co-IP), Western blotting (WB), and in vivo xenograft models were employed. Clinically, our findings revealed an upregulation of EIF3B expression in LSCC, with its abnormally high levels significantly correlating with poor survival outcomes among patients. Functionally, ablation of EIF3B potently inhibited cancer cell proliferation, colony formation, and migratory abilities. Mechanistically, EIF3B stabilized MAP2K2 via direct interaction with its P3 domain, inhibiting VHL-mediated ubiquitination at K169. Notably, MAP2K2 kinase activity was essential for EIF3B-driven ERK phosphorylation and downstream oncogenic signaling. Moreover, EIF3B overexpression accelerated tumor growth in xenograft models, which was rescued by MAP2K2 knockdown. In Conclusion, EIF3B promotes LSCC progression by stabilizing MAP2K2, activating the ERK/MAPK pathway, and disrupting VHL-mediated proteostasis. Targeting the EIF3B-MAP2K2 axis may offer therapeutic strategies for LSCC.

Laryngeal squamous cell carcinoma (LSCC) is a common malignant tumor originating from the mucosal epithelium of the larynx. MicroRNA (miR)-488-3p has non-negligible multifaceted roles in some types of cancer; however, its association with LSCC has not yet been reported. Our prior RNA sequencing data indicated that miR-488-3p expression is downregulated in LSCC tissue, yet the detailed function and regulatory mechanism of miR-488-3p in LSCC remain unknown. In the present study, quantitative PCR analysis corroborated the significant downregulation of miR-488-3p in LSCC tumor tissues, with this downregulation being strongly associated with malignant progression in LSCC. Furthermore, overexpression of miR-488-3p suppressed LSCC cell proliferation, colony formation, migration, invasion, xenograft tumor growth and epithelial-mesenchymal transition. Mechanistically, miR-488-3p directly interacted with the 3′ untranslated region of activin A receptor type 1C (ACVR1C) and downregulated ACVR1C expression. Functional experiments revealed that miR-488-3p suppressed the malignant phenotypes of LSCC via ACVR1C. Additionally, bioinformatics analysis coupled with chromatin immunoprecipitation assay revealed that myeloid ecotropic viral integration site 1 (MEIS1) promoted the expression of miR-488-3p transcriptionally by directly binding its promoter region. Collectively, the results demonstrated that miR-488-3p acts as a tumor suppressor molecule in LSCC, and a role was established for the MEIS1/miR-488-3p/ACVR1C axis in regulating LSCC progression, thus providing novel potential biomarkers and targets for patients with LSCC.

Laryngeal squamous cell carcinoma (LSCC), a complex cancer driven by genetic mutations, poses significant challenges for detection and treatment. Single-cell RNA sequencing (scRNA-seq) has emerged as a promising tool to uncover the cellular heterogeneity in cancer and identify novel therapeutic targets. In this study, we used scRNA-seq data (GSE252490) to explore molecular biomarkers for LSCC diagnosis and treatment. After processing and standardizing the data, we performed principal component analysis to identify highly variable genes. Cell clustering revealed 12 distinct clusters with unique molecular features. Differential gene expression analysis identified 6434 differentially expressed genes (DEGs), which were further analyzed using gene ontology enrichment to explore biological processes involved in LSCC progression. Protein-protein interaction (PPI) network analysis revealed 20 central genes associated with key cancer pathways. Pathway enrichment analysis through KEGG highlighted the involvement of these genes in various cancer-related pathways. Notably, genes such as CCL3, EPCAM, and IL8, with elevated expression, were linked to survival outcomes in LSCC. This comprehensive analysis provides valuable insights into the molecular landscape of LSCC, identifying potential biomarkers and therapeutic targets for improved diagnosis and treatment.

circHIPK2 promotes malignant progression of laryngeal squamous cell carcinoma through the miR-889-3p/MCTS1/IL-6 axis.

Integrative analysis of cuproptosis-related lncRNAs for prognostic risk assessment and tumor immune microenvironment evaluation in laryngeal squamous cell carcinoma.

MicroRNAs (miRNAs) have emerged as promising biomarkers for diagnosis and prognosis in laryngeal squamous cell carcinoma (LSCC). This study investigates the expression patterns of specific cancer-associated miRNAs in early and advanced stage LSCC to evaluate their potential role in disease progression. The expression levels of miRNA-21, miRNA-802, miRNA-29 and miRNA-9 were analysed in formalin-fixed paraffin-embedded (FFPE) tissues from 44 LSCC patients (20 early stage, 24 advanced stage) using quantitative multiplex RT-PCR. Tissue samples were analysed retrospectively. The expression level of hsa-miR-9a expression was significantly upregulated (5.2-fold) in advanced stage patients compared to the early stage group (p = 0.0088). Similarly, hsa-miR-802a showed significantly higher expression (9.2-fold) in advanced stage patients compared to early stage patients (p = 0.005). No significant differences in miRNA-21 and miRNA-29 expression levels were observed between the groups. As a result of the study, elevated miRNA levels in advanced stage patients can be used in targeted therapy and evaluated as a treatment option in LSCC patients.

Laryngeal squamous cell carcinoma (LSCC) is a highly aggressive malignancy with a rising incidence over time. The tumor microenvironment (TME) plays a crucial role in LSCC development, yet the precise cellular characteristics of laryngeal cancer and its TME remain unclear. Here, we employed single-cell RNA sequencing analysis to uncover the heterogeneous populations of tumor and immune cells and investigate the role of the TME in LSCC. This analysis revealed significant heterogeneity among malignant cells, T cells, and macrophages. Notably, regulatory T cells were markedly increased at tumor sites, and macrophage analysis identified an increased presence of the Macrophage-C1-C1QC subset with up-regulated PPIF expression. Bulk RNA-seq further confirmed PPIF up-regulation in exosomes derived from LSCC tissues. Consistently, survival analysis indicated that high PPIF expression was associated with poor prognosis in LSCC. Further analyses suggested that PPIF up-regulation in Macrophage-C1-C1QC cells was associated with the enhancement of their anti-inflammatory phenotype and the promotion of F11R-F11R signaling with malignant cells, allowing LSCC cells to evade macrophage-mediated cytotoxicity. Our study provides new insights into the cellular dynamics of LSCC and highlights the critical role of Macrophage-C1-C1QC and PPIF in LSCC progression, offering potential therapeutic targets for treatment.

Laryngeal squamous cell carcinoma (LSCC) exhibits aggressive growth, frequent recurrence, and a notable resistance to existing treatments. Building upon prior discoveries that identified junctional adhesion molecule 3 (JAM3) as a critical tumor suppressor in LSCC, this study delves into the transcriptional regulation by upstream stimulatory factor 1 (USF1) and its implications for LSCC pathogenesis. Employing dual-luciferase assays and chromatin immunoprecipitation-quantitative polymerase chain reaction (ChIP-qPCR), we confirmed USF1's direct binding to the E-box within the JAM3 promoter, thereby enhancing JAM3 expression in AMC-HN-8 and FD-LSC-1 cells. Complementary in vitro assays and in vivo experiments corroborated that USF1 overexpression markedly reduces tumor aggressiveness, linked to heightened JAM3 activity. Further analysis, including Western blot and immunohistochemistry of xenograft tumor tissues, revealed that increased JAM3, stimulated by USF1, activates the Hippo signaling pathway, underscoring its role in tumor suppression. These findings position USF1 and JAM3 as pivotal elements in the molecular framework of LSCC, suggesting their potential as targets for therapeutic intervention.