As the second most prevalent malignant tumor of head and neck, laryngeal squamous cell carcinoma (LSCC) imposes a substantial health burden on patients worldwide. Within recent years, resistance to oxidative stress and N6-methyladenosine (m6A) of RNA have been proved to be significantly involved in tumorigenesis. In current study, we investigated the oncogenic role of m6A modified long non coding RNAs (lncRNAs), specifically HOXA10-AS, and its downstream signaling pathway in the regulation of oxidative resistance in LSCC. Bioinformatics analysis revealed that heightened expression of HOXA10-AS was associated with the poor prognosis in LSCC patients, and N (6)-Methyladenosine (m6A) methyltransferase-like 3 (METTL3) was identified as a factor in promoting m6A modification of HOXA10-AS and further intensify its RNA stability. Mechanistically, HOXA10-AS was found to play as a competitive endogenous RNA (ceRNA) by sequestering miR-29 b-3p and preventing its downregulation of Integrin subunit alpha 6 (ITGA6), ultimately enhancing the oxidative resistance of tumor cells and promoting the malignant progression of LSCC. Furthermore, our research elucidated the mechanism by which ITGA6 accelerates Keap1 proteasomal degradation via enhancing TRIM25 expression, leading to increased Nrf2 stability and exacerbating its aberrant activation. Additionally, we demonstrated that ITGA6 enhances γ-secretase-mediated Notch signaling activation, ultimately promoting RBPJ-induced TRIM25 transcription. The current study provides the evidence supporting the effect of m6A modified HOXA10-AS and its downstream miR-29 b-3p/ITGA6 axis on regulating oxidative resistance and malignant progression in LSCC through the Notch and Keap1/Nrf2 pathways, and proposed that targeting this axis holds promise as a potential therapeutic approach for treating LSCC. 

m6A/HOXA10-AS/ITGA6 axis aggravates oxidative resistance and malignant progression of laryngeal squamous cell carcinoma through regulating Notch and Keap1/Nrf2 pathways.

Oral cancer accounts for 2% of cancer-related deaths globally, with over 90% of cases being oral cavity squamous cell carcinomas (OSCCs). Approximately 50% of patients with OSCC succumb to the disease within 5 years, primarily due to the advanced stage at which it is typically diagnosed. This underscores an urgent need to identify proteins related to OSCC progression to develop effective diagnostic and therapeutic strategies. 

Upregulation of ENAH by a PI3K/AKT/β-catenin cascade promotes oral cancer cell migration and growth via an ITGB5/Src axis

Arecoline, the main component of betel nut, induces malignant transformation of oral cells through complicated unclear mechanisms. Thus, we aimed to screen the key genes involved in Arecoline‐induced oral cancer and further verify their expressions and roles.

MYO1B as a prognostic biomarker and a therapeutic target in Arecoline‐associated oral carcinoma

Head and neck squamous cell carcinoma (HNSC) is one of the leading causes of cancer death globally, yet there are few useful biomarkers for early identification and prognostic prediction. Previous studies have confirmed that CCND1 amplification is closely associated with head and neck oncogenesis, and the present study explored the ceRNA network associated with CCND1. Gene expression profiling of the Head and Neck Squamous Cell Carcinoma (HNSC) project of The Cancer Genome Atlas (TCGA) program identified the TPRG1-AS1-hsa-miR-363-3P-MYO1B gene regulatory axis associated with CCND1. Further analysis of the database showed that MYOB was regulated by methylation in head and neck tumors, and functional enrichment analysis showed that MYO1B was involved in "actin filament organization" and "cadherin binding ". Immune infiltration analysis suggested that MYO1B may influence tumorigenesis and prognosis by regulating the immune microenvironment of HNSC. MYO1B enhanced tumor spread through the EMT approach, according to epithelial mesenchymal transition (EMT) characterisation. We analyzed both herbal and GSCALite databases and found that CCND1 and MYO1B have the potential as predictive biomarkers for the treatment of HNSC patients. RT-qPCR validated bioinformatic predictions of gene expression in vitro cell lines. In conclusion, we found a CCND1-related ceRNA network and identified the novel TPRG1-AS1-hsa-miR-363-3p-MYO1B pathway as a possible HNSC diagnostic biomarker and therapeutic target. 

CCND1-associated ceRNA network reveal the critical pathway of TPRG1-AS1-hsa-miR-363-3p-MYO1B as a prognostic marker for head and neck squamous cell carcinoma

Myosin superfamily, a large and diverse family of molecular motors important for cell motility and migration, has been illustrated to play contradictory roles during the development of several kinds of tumors. However, the function and prognostic values of MYOs in head and neck squamous cell carcinoma (HNSCC) still remain largely unknown. In the current manuscript, the expression levels and clinical data of MYOs in HNSCC were investigated by online databases, including Oncomine, GEPIA, GEO, TCGA, HPA, UALCAN, Kaplan-Meier plotter, and CancerSEA; we found that the expression levels of MYO1B, MYO5A, and MYO10 were significantly elevated in HNSCC tissues, which were also correlated with the unfavorable overall survival (OS) of the patients. Furthermore, MYO1B/MYO5A/MYO10 interacting genes were identified, and the protein-protein interaction (PPI) networks were constructed by STRING and GeneMANIA. The enrichment analysis revealed that MYO1B/MYO5A/MYO10 associated genes mainly participated in cell metastasis and EMT processes, which were also confirmed by cell functional experiments. At last, the ssGSEA method was conducted to investigate the extent of immune cell infiltration, and we found that both the expression of MYO1B/MYO5A/MYO10 were closely correlated with the infiltration of immune cells in HNSCC. These findings implied that MYO1B, MYO5A, and MYO10 as novel prognostic factors for HNSCC and provided new strategy for HNSCC treatment.

/pdf/comprehensive-landscape-of-prognostic-significance-and-k56qwig2.pdf

Comprehensive Landscape of Prognostic Significance and Immune Characteristics of Myosins in Squamous Cell Carcinoma of the Head and Neck

Deciphering the value of anoikis-related genes in prognosis, immune microenvironment, and drug sensitivity of laryngeal squamous cell carcinoma.

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

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Comprehensive Landscape of Prognostic Significance and Immune Characteristics of Myosins in Squamous Cell Carcinoma of the Head and Neck

Deciphering the value of anoikis-related genes in prognosis, immune microenvironment, and drug sensitivity of laryngeal squamous cell carcinoma.

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