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As the critical components of tumor microenvironment, cancer-associated fibroblasts (CAFs) support the development of various type of cancers, including laryngeal squamous cell carcinoma (LSCC), but the detailed molecular mechanisms by which cancer-associated fibroblasts interact with LSCC cells to facilitate its progression have not been fully uncovered. In the present study, by analyzing the contents from normal fibroblasts (NFs) and cancer-associated fibroblasts-derived extracellular vesicles (EVs) with Real-Time qPCR analysis, we found that the tumor-initiating LncRNA TUC338 was significantly upregulated in the cancer-associated fibroblasts-derived extracellular vesicles, compared to the normal fibroblasts-secreted extracellular vesicles. Further experiments confirmed that cancer-associated fibroblasts-derived extracellular vesicles promoted cell proliferation, colony formation abilities, epithelial-mesenchymal transition (EMT) and tumorigenesis of LSCC cells via delivering LncRNA TUC338. The mechanical experiments verified that LncRNA TUC338 was stabilized by METTL3/YTHDF1-mediated N6-methyladenosine (m6A) modifications, and elevated LncRNA TUC338 sponged miR-8485 to upregulate chromobox homolog 2 (CBX2) in LSCC cells in a competing endogenous RNA mechanisms-dependent manner. Moreover, our rescue experiments evidenced that cancer-associated fibroblasts-derived LncRNA TUC338-containing extracellular vesicles-induced supportive effects in LSCC aggressiveness were all abrogated by overexpressing miR-8485 and silencing CBX2. Collectively, this study is the first to identify a novel m6A/LncRNA TUC338/miR-8485/CBX2 axis in CAFs-EVs-mediated LSCC development, and to show its potential as a diagnostic biomarker for LSCC. • CAFs-derived extracellular vesicles enhanced cancer aggressiveness of LSCC via delivering TUC338. • METTL3/YTHDF1-mediated m6A modifications are essential for sustaining the stability and expression of TUC338. • TUC338 upregulated CBX2 via sponging miR-8485 in a ceRNA-dependent manner. • TUC338-EVs promoted LSCC progression through modulating the miR-8485/CBX2 axis. [ABSTRACT FROM AUTHOR]

Background: To investigate the effect of DACH1 over-expression on proliferation and invasion of laryngeal squamous cell carcinoma (LSCC). Methods: The 120 cases of LSCC tumors and 114 adjacent non-neoplastic tissues were collected to detect the expression of DACH1 by immunohistochemistry. The changes of DACH1 expression from each group were assessed and correlated to the clinical parameters of the patients. Plasmid-DACH1 was transfected into Hep-2 cells to up-regulate the expression of DACH1C. Real-time PCR, Western blot, CCK8 and transwell assay were used to verify the cell proliferation and invasion after plasmid-DACH1 transfection. Results: The results indicated that DACH1 was downregulated in LSCC tissues as compared to corresponding adjacent non-neoplastic tissues. Decreased expression of DACH1 was found in the tumors upraglottic tumor, lymph node metastases, T3–4 stage and advanced clinical stage. In Hep-2 cells, transfection with plasmid-DACH1 could suppress cell proliferation, invasion and induce G1 phase extension in cell cycle. Conclusions: DACH1 may act as a tumor suppressor gene and could be a potential target for therapeutic intervention of LSCC. [ABSTRACT FROM AUTHOR]