Nasopharyngeal carcinoma derived exosomes regulate the proliferation and migration of nasopharyngeal carcinoma cells by mediating the miR-99a-5p BAZ2A axis

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 microRNA...

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Main Authors: Xiao-jun Zhou, Hang-min Xu, Guo-sen Huang, Bao-rui Lin
Format: Article
Language:English
Published: Elsevier 2024-01-01
Series:Brazilian Journal of Otorhinolaryngology
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S1808869423001118
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author Xiao-jun Zhou
Hang-min Xu
Guo-sen Huang
Bao-rui Lin
author_facet Xiao-jun Zhou
Hang-min Xu
Guo-sen Huang
Bao-rui Lin
author_sort Xiao-jun Zhou
collection DOAJ
description 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)-1β and Nuclear Transcription Factor-κB (NF-κB) (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.
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spelling doaj.art-7062f7b060374d3f994f5d1b326ec8222024-01-26T05:32:36ZengElsevierBrazilian Journal of Otorhinolaryngology1808-86942024-01-01901101343Nasopharyngeal carcinoma derived exosomes regulate the proliferation and migration of nasopharyngeal carcinoma cells by mediating the miR-99a-5p BAZ2A axisXiao-jun Zhou0Hang-min Xu1Guo-sen Huang2Bao-rui Lin3Integrated Hospital of Traditional Chinese Medicine of Southern Medical University, Department of Otolaryngology, Guangzhou, China; Corresponding author.Zhongshan Traditional Chinese Medicine Hospital Affiliated to Guangzhou University of Chinese Medicine, Zhongshan, ChinaZhongshan Traditional Chinese Medicine Hospital Affiliated to Guangzhou University of Chinese Medicine, Zhongshan, ChinaZhongshan Traditional Chinese Medicine Hospital Affiliated to Guangzhou University of Chinese Medicine, Zhongshan, ChinaObjectives: 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)-1β and Nuclear Transcription Factor-κB (NF-κB) (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.http://www.sciencedirect.com/science/article/pii/S1808869423001118Nasopharyngeal carcinomaExosomesMiR-99a-5pBAZ2AProliferationMigration
spellingShingle Xiao-jun Zhou
Hang-min Xu
Guo-sen Huang
Bao-rui Lin
Nasopharyngeal carcinoma derived exosomes regulate the proliferation and migration of nasopharyngeal carcinoma cells by mediating the miR-99a-5p BAZ2A axis
Brazilian Journal of Otorhinolaryngology
Nasopharyngeal carcinoma
Exosomes
MiR-99a-5p
BAZ2A
Proliferation
Migration
title Nasopharyngeal carcinoma derived exosomes regulate the proliferation and migration of nasopharyngeal carcinoma cells by mediating the miR-99a-5p BAZ2A axis
title_full Nasopharyngeal carcinoma derived exosomes regulate the proliferation and migration of nasopharyngeal carcinoma cells by mediating the miR-99a-5p BAZ2A axis
title_fullStr Nasopharyngeal carcinoma derived exosomes regulate the proliferation and migration of nasopharyngeal carcinoma cells by mediating the miR-99a-5p BAZ2A axis
title_full_unstemmed Nasopharyngeal carcinoma derived exosomes regulate the proliferation and migration of nasopharyngeal carcinoma cells by mediating the miR-99a-5p BAZ2A axis
title_short Nasopharyngeal carcinoma derived exosomes regulate the proliferation and migration of nasopharyngeal carcinoma cells by mediating the miR-99a-5p BAZ2A axis
title_sort nasopharyngeal carcinoma derived exosomes regulate the proliferation and migration of nasopharyngeal carcinoma cells by mediating the mir 99a 5p baz2a axis
topic Nasopharyngeal carcinoma
Exosomes
MiR-99a-5p
BAZ2A
Proliferation
Migration
url http://www.sciencedirect.com/science/article/pii/S1808869423001118
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