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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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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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. |
format | Online Article Text |
id | pubmed-8554159 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
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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