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The present study aimed to investigate LINC00278 expression in laryngeal squamous cell carcinoma (LSCC) and its involvement in the process of proliferation, migration, and invasion, providing a rationale for mining potential diagnostic and therapeutic targets of LSCC. Univariate and multivariate Cox regression analyses were performed to identify optimal prognostic lncRNAs. MTS, colony formation, wound healing, and Transwell invasion assays were used to determine the effects of LINC00278 overexpression on the proliferation, migration, and invasion of cancer cells. The expressions of signaling pathway-related proteins and epithelial-mesenchymal transition (EMT) marker proteins were detected using western blot. The chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays were performed to demonstrate the binding of ETS proto-oncogene 1, transcription factor (ETS1), and LINC00278 promoter region. The molecular targets of LINC00278 were identified by RNA sequencing analysis and co-expression analysis. Kaplan-Meier analysis and CIBERSORT algorithm were used to analyze survival and immune cell infiltration based on LINC00278, COL4A1, and COL4A2. Multivariate Cox regression was used to establish a six-gene prognostic model. LINC00278 expression was low in LSCC tissues, and it was significantly associated with the TNM (tumors/nodes/metastases) stage (p<0.001), lymphatic metastasis (p<0.01), and pathological differentiation (p<0.01). LINC00278 overexpression significantly reduced LSCC cell proliferation, migration, and invasion in TU686, TU177, and AMC-HN-8 cell lines. E-cadherin protein expression was increased, while N-cadherin, Vimentin, Zeb1, and Snail protein expression was decreased in the LINC00278 group, compared to the pcDNA3.1 group. Additionally, in AMC-HN-8 and FaDu cell lines, the LINC00278-treated group had significantly lower p-AKT and p-mTOR protein levels than the control group. ETS1 is a direct transcriptional regulator of the LINC00278 gene based on luciferase reporter assays and ChIP experiments. Western blot analysis demonstrated that high LINC00278 expression inhibited both ETS1 expression and phosphorylation. COL4A1/COL4A2 were identified as potential downstream targets of LINC00278. Meanwhile, the LINC00278/COL4A1/COL4A2-dominated low-risk group showed higher antigen-presenting activity and a higher immune score than the high-risk group. The findings indicated that ETS1 upregulated LINC00278 expression on the Y chromosome, which in turn inhibited LSCC growth in vivo and in vitro by inhibiting the AKT/mTOR signaling pathway via downregulation of COL4A1/COL4A2. [ABSTRACT FROM AUTHOR]

This study aimed to elucidate the potential genes of the matrix metalloproteinase (MMP) family, responsible for the progression of laryngeal squamous cell carcinoma (LSCC). Besides, we ascertained the changes in common malignant behaviors in vitro by knocking down MMP1. TCGA, GEO, Oncomine, and microarray data were conducted to analyze the expression levels of MMPs and to find tissue-specific genes in LSCC. Univariate and multivariate Cox regression analyses were established in the construction of a prognostic model based on expression profiles and clinical information of LSCC in TCGA. We then comprehensively analyzed survival, co-expression network, and immune infiltration based on a prognostic model by Kaplan-Meier analysis, WGCNA, and CIBERSORT. Thereafter, qRT-PCR, proliferation, Transwell, and woundhealing assays were used to assess the accuracy of the bioinformatics data. A total of seven genes in the MMP family were identiThed as differentially expressed genes (DEGs) by integrating three public databases and microarray data. Additionally, multivariate Cox regression was used to establish a four-gene (MMP1/3/8/10) prognostic model, which exhibited a better predictive accuracy than the TNM (tumors/nodes/metastases) based model. The prognostic model was related to plasma cells, CD8+ T cells, follicular helper T cells, resting NK cells, and M0 macrophages infiltration. The expression of MMP1, MMP3, and MMP10 was the highest in head and neck squamous cell carcinoma (HNSC) compared to other cancer in the Oncomine and GEPIA dataset. Further, MMP1 demonstrated significant upregulation in 40 paired LSCC tissues. Eventually, MMP1 downregulation inhibited cell viability, colony formation, and cell migration in TU686 and FaDu cells. Our findings suggest that the four-gene signature might be associated with the prognosis. Further, we revealed that MMP1 is a pivotal biomarker for the biotherapy and prognostic evaluation of patients with LSCC. [ABSTRACT FROM AUTHOR]