PMID- 37777021 OWN - NLM STAT- MEDLINE DCOM- 20231206 LR - 20231216 IS - 1096-1194 (Electronic) IS - 0890-8508 (Linking) VI - 72 DP - 2023 Dec TI - Cancer-associated fibroblasts secret extracellular vesicles to support cell proliferation and epithelial-mesenchymal transition in laryngeal squamous cell carcinoma. PG - 101934 LID - S0890-8508(23)00043-9 [pii] LID - 10.1016/j.mcp.2023.101934 [doi] AB - 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. CI - Copyright (c) 2023 The Authors. Published by Elsevier Ltd.. All rights reserved. FAU - Li, Tingting AU - Li T AD - Department of Otolaryngology-Head and Neck Surgery, The Fourth Affiliated Hospital of Harbin Medical University, Yiyuan Street No. 37, Nangang District, Harbin, 150001, Heilongjiang, China. Electronic address: 120001998@hrbmu.edu.cn. FAU - Tian, Linli AU - Tian L AD - Department of Otolaryngology-Head and Neck Surgery, The Second Affiliated Hospital of Harbin Medical University, Xuefu Road No. 246, Nangang District, Harbin, 150086, Heilongjiang, China. Electronic address: Tianll78@163.com. FAU - Cao, Jing AU - Cao J AD - Department of Otolaryngology-Head and Neck Surgery, The Second Affiliated Hospital of Harbin Medical University, Xuefu Road No. 246, Nangang District, Harbin, 150086, Heilongjiang, China. Electronic address: Caoj001989@163.com. FAU - Liu, Ming AU - Liu M AD - Department of Otolaryngology-Head and Neck Surgery, The Second Affiliated Hospital of Harbin Medical University, Xuefu Road No. 246, Nangang District, Harbin, 150086, Heilongjiang, China. Electronic address: lmdoctor@hrbmu.edu.cn. LA - eng PT - Journal Article DEP - 20231009 PL - England TA - Mol Cell Probes JT - Molecular and cellular probes JID - 8709751 RN - 0 (MicroRNAs) RN - 0 (RNA, Long Noncoding) RN - EC 2.1.1.62 (METTL3 protein, human) RN - EC 2.1.1.- (Methyltransferases) SB - IM MH - Humans MH - Squamous Cell Carcinoma of Head and Neck/genetics MH - *MicroRNAs/genetics/metabolism MH - *Cancer-Associated Fibroblasts/metabolism MH - Cell Line, Tumor MH - Epithelial-Mesenchymal Transition/genetics MH - *RNA, Long Noncoding/genetics/metabolism MH - Cell Proliferation/genetics MH - *Extracellular Vesicles/metabolism MH - *Head and Neck Neoplasms/genetics MH - Gene Expression Regulation, Neoplastic MH - Tumor Microenvironment MH - Methyltransferases/genetics/metabolism OTO - NOTNLM OT - CBX2 OT - Cancer-associated fibroblasts OT - Competing endogenous RNA OT - Extracellular vesicles OT - LncRNA TUC338 EDAT- 2023/10/01 04:44 MHDA- 2023/12/06 06:42 CRDT- 2023/09/30 19:14 PHST- 2023/05/18 00:00 [received] PHST- 2023/09/28 00:00 [revised] PHST- 2023/09/28 00:00 [accepted] PHST- 2023/12/06 06:42 [medline] PHST- 2023/10/01 04:44 [pubmed] PHST- 2023/09/30 19:14 [entrez] AID - S0890-8508(23)00043-9 [pii] AID - 10.1016/j.mcp.2023.101934 [doi] PST - ppublish SO - Mol Cell Probes. 2023 Dec;72:101934. doi: 10.1016/j.mcp.2023.101934. Epub 2023 Oct 9.