PMID- 35545731 OWN - NLM STAT- MEDLINE DCOM- 20220627 LR - 20220628 IS - 1749-0774 (Electronic) IS - 0914-7470 (Linking) VI - 35 IP - 4 DP - 2022 Jul TI - Serum-derived extracellular vesicles mediate Smad4 expression through shuttling microRNA-27a in the progression of laryngeal squamous cell carcinoma. PG - 1084-1099 LID - 10.1007/s13577-022-00712-6 [doi] AB - Serum-derived extracellular vesicles (EVs) containing non-coding RNAs have been indicated to serve as diagnostic and prognostic biomarkers for laryngeal squamous cell carcinoma (LSCC), while their functional role remains to be explored. Here, we summarize the possible mechanism explaining the laryngeal carcinogenesis and the associated changes with the involvement of extracellular microRNA (miR)-27a from serum of LSCC patients. Serum-derived EVs from LSCC patients were found to increase the proliferative activity and decreased the apoptotic activity of LSCC cells. miRNA microarrays revealed that miR-27a expression was elevated after EV treatment. miR-27a expression was elevated in LSCC tissues and predicted a poor prognosis for patients. Downregulation of miR-27a inhibited the effect of EVs to reduce the activity of LSCC cells in vitro and to suppress tumor development in vivo. miR-27a targeted SMAD family member 4 (Smad4) to mediate the Wnt/beta-catenin pathway, which was induced under the influence of EVs. Smad4 was downregulated in LSCC tissues, and simultaneous overexpression of miR-27a and Smad4 resulted in reduced cell activity and tumorigenicity. In conclusion, serum-derived EVs support the laryngeal carcinogenesis at least partially via transferring miR-27a. miR-27a targets Smad4 and is a biomarker to predict LSCC prognosis. CI - (c) 2022. The Author(s) under exclusive licence to Japan Human Cell Society. FAU - Shuang, Yu AU - Shuang Y AD - Department of Otorhinolaryngology Head and Neck Surgery, The Second Hospital of Tianjin Medical University, No. 23, Pingjiang Road, Tianjin, 300211, People's Republic of China. yushuang_11252@126.com. FAU - Yao, Xiaofeng AU - Yao X AD - Department of Maxillofacial and Otorhinolaryngology Head and Neck Surgery, Tianjin Medical University Cancer Institute and Hospital, Tianjing, 300202, People's Republic of China. FAU - Liu, Jing AU - Liu J AD - Department of Otorhinolaryngology Head and Neck Surgery, The Second Hospital of Tianjin Medical University, No. 23, Pingjiang Road, Tianjin, 300211, People's Republic of China. FAU - Niu, Juntao AU - Niu J AD - Department of Otorhinolaryngology Head and Neck Surgery, The Second Hospital of Tianjin Medical University, No. 23, Pingjiang Road, Tianjin, 300211, People's Republic of China. FAU - Guo, Wenyu AU - Guo W AD - Department of Otorhinolaryngology Head and Neck Surgery, The Second Hospital of Tianjin Medical University, No. 23, Pingjiang Road, Tianjin, 300211, People's Republic of China. FAU - Li, Chao AU - Li C AD - Department of Otorhinolaryngology Head and Neck Surgery, The Second Hospital of Tianjin Medical University, No. 23, Pingjiang Road, Tianjin, 300211, People's Republic of China. LA - eng GR - 2020LC08/Clinical medicine research project of the second hospital of Tianjin Medical University/ PT - Journal Article DEP - 20220512 PL - Japan TA - Hum Cell JT - Human cell JID - 8912329 RN - 0 (MicroRNAs) RN - 0 (SMAD4 protein, human) RN - 0 (Smad4 Protein) SB - IM MH - Carcinogenesis/genetics MH - *Carcinoma, Squamous Cell/pathology MH - Cell Line, Tumor MH - Cell Proliferation/genetics MH - *Extracellular Vesicles/genetics/metabolism MH - Gene Expression Regulation, Neoplastic/genetics MH - *Head and Neck Neoplasms/genetics MH - Humans MH - *Laryngeal Neoplasms/genetics/metabolism/pathology MH - *MicroRNAs/genetics/metabolism MH - Smad4 Protein/genetics/metabolism MH - Squamous Cell Carcinoma of Head and Neck/genetics OTO - NOTNLM OT - Extracellular vesicles OT - Laryngeal squamous cell carcinoma OT - Smad4 OT - Wnt/beta-catenin pathway OT - microRNA-27a EDAT- 2022/05/12 06:00 MHDA- 2022/06/28 06:00 CRDT- 2022/05/11 23:20 PHST- 2021/11/02 00:00 [received] PHST- 2022/04/25 00:00 [accepted] PHST- 2022/05/12 06:00 [pubmed] PHST- 2022/06/28 06:00 [medline] PHST- 2022/05/11 23:20 [entrez] AID - 10.1007/s13577-022-00712-6 [pii] AID - 10.1007/s13577-022-00712-6 [doi] PST - ppublish SO - Hum Cell. 2022 Jul;35(4):1084-1099. doi: 10.1007/s13577-022-00712-6. Epub 2022 May 12.