Hypoxia combined with radiation reverses migration and invasion of head and neck squamous cell carcinoma by remodeling extracellular vesicle-mediated transfer of miR-23b-5p from cancer-associated fibroblasts  

作　　者：Chuanshi He Mingzhe Xie Zhimi Zhang Bangrong Cao Huaichao Luo Guiquan Zhu Shun Lu Ling Li 

机构地区：[1]Sichuan Clinical Research Center for Cancer,Sichuan Cancer Hospital&Institute,Sichuan Cancer Center,Affiliated Cancer Hospital of University of Electronic Science and Technology of China,Chengdu,Sichuan,China [2]State Key Laboratory of Oral Diseases&National Clinical Research Centre for Oral Diseases,Department of Head and Neck Oncology,West China Hospital of Stomatology,Sichuan University,Chengdu,Sichuan,China

出　　处：《Malignancy Spectrum》2024年第4期275-289,共15页肿瘤学全景(英文)

基　　金：supported by the National Natural Science Foundation of China(81972541,81872196,and 82273307);the Natural Science Foundation of Sichuan Province(2022NSFSC0681 and 2022NSFSC0632)。

摘　　要：Background:Cancer-associated fibroblasts(CAFs),the main matrix components in the tumor microenvironment(TME),play a crucial role in tumor progression.Extracellular vesicles(EVs)as main mediators in intercellular communication can be regulated by hypoxia or radiation.Methods:CAFs were extracted from head and neck squamous cell carcinoma(HNSCC)tissues and CAF-derived EVs were collected by ultracentrifugation.Bioinformatics analysis determined the role of poly(U)-specific endonuclease(ENDOU)on HNSCC progression and confirmed that ENDOU inhibited HNSCC progression by overexpressing ENDOU in HNSCC.Dual-luciferase activity report assay confirmed that miR-23b-5p was involved in the regulation of ENDOU expression.The migration and invasion of HNSCC cells were verified by transwell assay.Furthermore,tumor-bearing mouse models were used to demonstrate the potential of EVs loaded with miR-23b-5p in HNSCC to promote tumor progression.Results:Our results showed that ENDOU was downregulated in HNSCC and inhibited HNSCC migration and invasion.Hypoxia and radiotherapy reversed CAF-derived EVs to promote migration and invasion of HNSCC.Mechanically,hypoxia and radiation downregulated miR-23b-5p in CAFderived EVs and then restored ENDOU expression in HNSCC.Finally,CAF-derived EVs carrying miR-23b-5p promoted the progression of HNSCC cells in vivo by regulating ENDOU expression.Conclusion:This study demonstrated that hypoxia combined with radiation reverses the promoting effect of CAFs on HNSCC migration and invasion by reducing the delivery of miR-23b-5p by CAF-derived EVs to decrease the inhibitory effect of ENDOU expression in HNSCC.The results provide a new perspective for better understanding the role of stromal components in TME in tumor regulation.Furthermore,the results provide a strong basis for the possibility of ENDOU as a biomarker for HNSCC.

关 键 词：cancer-associated fibroblast extracellular vesicle HYPOXIA RADIOTHERAPY head and neck squamous cell carcinoma 

分 类 号：R73[医药卫生—肿瘤]