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MicroRNA-483-5p Predicts Poor Prognosis and Promotes Cancer Metastasis by Targeting EGR3 in Nasopharyngeal Carcinoma

BACKGROUND: MicroRNAs, as small non-coding RNAs, play an important role in tumorigenesis. MiR-483-5p was found to have a significant increase as a diagnostic biomarker of nasopharyngeal carcinoma (NPC), not only in plasma from NPC patients but also in tumor cell lines and biopsy tissues in our previ...

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Autores principales: Li, Xi-Zhao, Tu, Yi-Jun, Zhou, Ting, Zhang, Jiang-Bo, Xiao, Ruo-Wen, Yang, Da-Wei, Zhang, Pei-Fen, You, Peng-Tao, Zheng, Xiao-Hui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8554159/
https://www.ncbi.nlm.nih.gov/pubmed/34722264
http://dx.doi.org/10.3389/fonc.2021.720835
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author Li, Xi-Zhao
Tu, Yi-Jun
Zhou, Ting
Zhang, Jiang-Bo
Xiao, Ruo-Wen
Yang, Da-Wei
Zhang, Pei-Fen
You, Peng-Tao
Zheng, Xiao-Hui
author_facet Li, Xi-Zhao
Tu, Yi-Jun
Zhou, Ting
Zhang, Jiang-Bo
Xiao, Ruo-Wen
Yang, Da-Wei
Zhang, Pei-Fen
You, Peng-Tao
Zheng, Xiao-Hui
author_sort Li, Xi-Zhao
collection PubMed
description BACKGROUND: MicroRNAs, as small non-coding RNAs, play an important role in tumorigenesis. MiR-483-5p was found to have a significant increase as a diagnostic biomarker of nasopharyngeal carcinoma (NPC), not only in plasma from NPC patients but also in tumor cell lines and biopsy tissues in our previous study. However, its function and mechanism in NPC are still unclear. METHODS: Tissue microarray including 178 primary NPC and 35 adjacent non-cancerous nasopharyngeal mucosal tissues was used to further validate the overexpression of miR-483-5p. Wound healing and invasion assays were conducted to verify its biological function. RNA sequencing (RNA-seq) and dual-luciferase reporter assay was performed to explore its target, and it was verified in fresh biopsy tissues from 23 NPC patients and 9 patients with chronic nasopharyngitis. RESULTS: MiR-483-5p was highly expressed in NPC tissues than in adjacent non-cancerous tissues. It was found to have a significant correlation with poor overall survival (OS) [hazard ratio (HR) = 2.89, 95% confidence interval (CI) = 1.00–8.35, p = 0.041] and progression-free survival (PFS) (HR = 1.95, 95%CI = 1.06–3.60, p = 0.029) of NPC patients. Silencing of its expression inhibited the migratory and invasive capacities of NPC cells in vitro. EGR3 (early growth response 3) was identified as a direct target, and inhibiting miR-483-5p expression markedly enhanced the expression of EGR3 at both the mRNA and protein levels. Besides, a significant decrease of EGR3 expression was found in fresh biopsy tissues from NPC patients, in contrast to miR-483-5p expression. Furthermore, directly decreasing the expression of EGR3 could enhance the migration and invasion of NPC cells. CONCLUSION: The newly identified miR-483-5p/EGR3 pathway provides further insights into the development and metastasis of NPC and may provide a potential therapeutic target for NPC treatment in order to improve survival of NPC patients.
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spelling pubmed-85541592021-10-30 MicroRNA-483-5p Predicts Poor Prognosis and Promotes Cancer Metastasis by Targeting EGR3 in Nasopharyngeal Carcinoma Li, Xi-Zhao Tu, Yi-Jun Zhou, Ting Zhang, Jiang-Bo Xiao, Ruo-Wen Yang, Da-Wei Zhang, Pei-Fen You, Peng-Tao Zheng, Xiao-Hui Front Oncol Oncology BACKGROUND: MicroRNAs, as small non-coding RNAs, play an important role in tumorigenesis. MiR-483-5p was found to have a significant increase as a diagnostic biomarker of nasopharyngeal carcinoma (NPC), not only in plasma from NPC patients but also in tumor cell lines and biopsy tissues in our previous study. However, its function and mechanism in NPC are still unclear. METHODS: Tissue microarray including 178 primary NPC and 35 adjacent non-cancerous nasopharyngeal mucosal tissues was used to further validate the overexpression of miR-483-5p. Wound healing and invasion assays were conducted to verify its biological function. RNA sequencing (RNA-seq) and dual-luciferase reporter assay was performed to explore its target, and it was verified in fresh biopsy tissues from 23 NPC patients and 9 patients with chronic nasopharyngitis. RESULTS: MiR-483-5p was highly expressed in NPC tissues than in adjacent non-cancerous tissues. It was found to have a significant correlation with poor overall survival (OS) [hazard ratio (HR) = 2.89, 95% confidence interval (CI) = 1.00–8.35, p = 0.041] and progression-free survival (PFS) (HR = 1.95, 95%CI = 1.06–3.60, p = 0.029) of NPC patients. Silencing of its expression inhibited the migratory and invasive capacities of NPC cells in vitro. EGR3 (early growth response 3) was identified as a direct target, and inhibiting miR-483-5p expression markedly enhanced the expression of EGR3 at both the mRNA and protein levels. Besides, a significant decrease of EGR3 expression was found in fresh biopsy tissues from NPC patients, in contrast to miR-483-5p expression. Furthermore, directly decreasing the expression of EGR3 could enhance the migration and invasion of NPC cells. CONCLUSION: The newly identified miR-483-5p/EGR3 pathway provides further insights into the development and metastasis of NPC and may provide a potential therapeutic target for NPC treatment in order to improve survival of NPC patients. Frontiers Media S.A. 2021-10-15 /pmc/articles/PMC8554159/ /pubmed/34722264 http://dx.doi.org/10.3389/fonc.2021.720835 Text en Copyright © 2021 Li, Tu, Zhou, Zhang, Xiao, Yang, Zhang, You and Zheng https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Li, Xi-Zhao
Tu, Yi-Jun
Zhou, Ting
Zhang, Jiang-Bo
Xiao, Ruo-Wen
Yang, Da-Wei
Zhang, Pei-Fen
You, Peng-Tao
Zheng, Xiao-Hui
MicroRNA-483-5p Predicts Poor Prognosis and Promotes Cancer Metastasis by Targeting EGR3 in Nasopharyngeal Carcinoma
title MicroRNA-483-5p Predicts Poor Prognosis and Promotes Cancer Metastasis by Targeting EGR3 in Nasopharyngeal Carcinoma
title_full MicroRNA-483-5p Predicts Poor Prognosis and Promotes Cancer Metastasis by Targeting EGR3 in Nasopharyngeal Carcinoma
title_fullStr MicroRNA-483-5p Predicts Poor Prognosis and Promotes Cancer Metastasis by Targeting EGR3 in Nasopharyngeal Carcinoma
title_full_unstemmed MicroRNA-483-5p Predicts Poor Prognosis and Promotes Cancer Metastasis by Targeting EGR3 in Nasopharyngeal Carcinoma
title_short MicroRNA-483-5p Predicts Poor Prognosis and Promotes Cancer Metastasis by Targeting EGR3 in Nasopharyngeal Carcinoma
title_sort microrna-483-5p predicts poor prognosis and promotes cancer metastasis by targeting egr3 in nasopharyngeal carcinoma
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8554159/
https://www.ncbi.nlm.nih.gov/pubmed/34722264
http://dx.doi.org/10.3389/fonc.2021.720835
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