PMID- 37925811 OWN - NLM STAT- MEDLINE DCOM- 20240129 LR - 20240206 IS - 1808-8686 (Electronic) IS - 1808-8694 (Print) IS - 1808-8686 (Linking) VI - 90 IP - 1 DP - 2024 Jan-Feb TI - Nasopharyngeal carcinoma derived exosomes regulate the proliferation and migration of nasopharyngeal carcinoma cells by mediating the miR-99a-5p BAZ2A axis. PG - 101343 LID - S1808-8694(23)00111-8 [pii] LID - 10.1016/j.bjorl.2023.101343 [doi] LID - 101343 AB - OBJECTIVES: Nasopharyngeal Carcinoma (NPC) is a common malignant tumor of nasopharyngeal mucosal epithelium in clinical practice. Radiotherapy and chemotherapy are the main treatment methods at present, but the therapeutic effect is still unsatisfactory. Studies have shown that exosomes and microRNAs (miRNAs) play an important role in the development of cancer. Therefore, this study aimed to investigate the effects of NPC derived exosomes on NPC and their molecular mechanisms. METHODS: Serum was collected from healthy subjects, Epstein-Barr Virus (EBV) infected patients and NPC patients (n = 9 group) and exosomes were extracted separately. High-throughput sequencing of exosomes was performed to screen differentially expressed miRNAs. The function of the screened miRNA was identified by treating NPC cells with exosomes. The target gene of miRNA was identified using the dual-luciferase assay. Real-Time quantitative Polymerase Chain Reaction (RT-qPCR) was used to determine the levels of miR-99a-5p and Bromodomain Adjacent Tozinc finger domain protein 2A (BAZ2A). Cell Counting Kit-8 assay, flow cytometry, and wound healing assay were utilized to detect cell viability, cell cycle and apoptosis, and migration ability. The protein levels were evaluated by Western blot. RESULTS: MiR-99a-5p was identified as the most significant differentially expressed miRNA in exosomes (p < 0.05). The proliferation and migration of NPC cells were extremely facilitated by exosomes, accompanied by the suppressed apoptosis, upregulated BAZ2A, Monocyte Chemotactic Protein-1 (MCP1), and Vascular Endothelial Growth Factor A (VEGFA), and downregulation of Interleukin (IL)-1beta and Nuclear Transcription Factor-kappaB (NF-kappaB) (p < 0.05). BAZ2A was a target gene of miR-99a-5p. Furthermore, the regulatory effect of exosomes on the proliferation, migration, and apoptosis was significantly abolished by overexpression of miR-99a-5p or downregulation of BAZ2A (p < 0.05). CONCLUSION: NPC derived exosomes facilitated the proliferation and migration of NPC through regulating the miR-99a-5p/BAZ2A axis. CI - Copyright (c) 2023 Associacao Brasileira de Otorrinolaringologia e Cirurgia Cervico-Facial. Published by Elsevier Espana S.L.U. All rights reserved. FAU - Zhou, Xiao-Jun AU - Zhou XJ AD - Integrated Hospital of Traditional Chinese Medicine of Southern Medical University, Department of Otolaryngology, Guangzhou, China. Electronic address: zd1232@126.com. FAU - Xu, Hang-Min AU - Xu HM AD - Zhongshan Traditional Chinese Medicine Hospital Affiliated to Guangzhou University of Chinese Medicine, Zhongshan, China. FAU - Huang, Guo-Sen AU - Huang GS AD - Zhongshan Traditional Chinese Medicine Hospital Affiliated to Guangzhou University of Chinese Medicine, Zhongshan, China. FAU - Lin, Bao-Rui AU - Lin BR AD - Zhongshan Traditional Chinese Medicine Hospital Affiliated to Guangzhou University of Chinese Medicine, Zhongshan, China. LA - eng PT - Journal Article DEP - 20231011 PL - Brazil TA - Braz J Otorhinolaryngol JT - Brazilian journal of otorhinolaryngology JID - 101207337 RN - 0 (Vascular Endothelial Growth Factor A) RN - 0 (MicroRNAs) RN - 0 (BAZ2A protein, human) RN - 0 (Bromodomain Containing Proteins) RN - 0 (Chromosomal Proteins, Non-Histone) SB - IM MH - Humans MH - Nasopharyngeal Carcinoma/pathology MH - Vascular Endothelial Growth Factor A/genetics/metabolism MH - *Exosomes/genetics/metabolism/pathology MH - *Epstein-Barr Virus Infections/genetics MH - Cell Line, Tumor MH - Cell Proliferation MH - Herpesvirus 4, Human/genetics/metabolism MH - *MicroRNAs/genetics/metabolism MH - *Nasopharyngeal Neoplasms/genetics/pathology MH - Gene Expression Regulation, Neoplastic MH - Bromodomain Containing Proteins MH - Chromosomal Proteins, Non-Histone/genetics/metabolism PMC - PMC10654546 OTO - NOTNLM OT - BAZ2A OT - Exosomes OT - MiR-99a-5p OT - Migration OT - Nasopharyngeal carcinoma OT - Proliferation EDAT- 2023/11/06 00:41 MHDA- 2024/01/29 06:42 PMCR- 2023/10/11 CRDT- 2023/11/05 18:05 PHST- 2023/07/09 00:00 [received] PHST- 2023/09/17 00:00 [revised] PHST- 2023/10/02 00:00 [accepted] PHST- 2024/01/29 06:42 [medline] PHST- 2023/11/06 00:41 [pubmed] PHST- 2023/11/05 18:05 [entrez] PHST- 2023/10/11 00:00 [pmc-release] AID - S1808-8694(23)00111-8 [pii] AID - 101343 [pii] AID - 10.1016/j.bjorl.2023.101343 [doi] PST - ppublish SO - Braz J Otorhinolaryngol. 2024 Jan-Feb;90(1):101343. doi: 10.1016/j.bjorl.2023.101343. Epub 2023 Oct 11.