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Elevated expression of MKRN3 in squamous cell carcinoma of the head and neck and its clinical significance
BACKGROUND: Squamous cell carcinoma of the head and neck (SCCHN) is one of the most common types of cancer that cause a substantial number of cancer-related deaths. Our previous study has revealed that makorin ring finger protein 3 (MKRN3) may act as a key regulator of the SCCHN tumorigenesis; howev...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8543891/ https://www.ncbi.nlm.nih.gov/pubmed/34689784 http://dx.doi.org/10.1186/s12935-021-02271-6 |
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author | Zhang, Shuiting Liu, Chao Li, Guo Liu, Yong Wang, Xingwei Qiu, Yuanzheng |
author_facet | Zhang, Shuiting Liu, Chao Li, Guo Liu, Yong Wang, Xingwei Qiu, Yuanzheng |
author_sort | Zhang, Shuiting |
collection | PubMed |
description | BACKGROUND: Squamous cell carcinoma of the head and neck (SCCHN) is one of the most common types of cancer that cause a substantial number of cancer-related deaths. Our previous study has revealed that makorin ring finger protein 3 (MKRN3) may act as a key regulator of the SCCHN tumorigenesis; however, its specific role in SCCHN progression has not been reported. METHODS: The Cancer Genome Atlas (TCGA) data analysis and quantitative polymerase chain reaction (qPCR) were used to quantify the MKRN3 mRNA expression levels in SCCHN; immunohistochemical staining or immunoblotting analyses were performed to detect MKRN3 protein expression. Kaplan–Meier plotter was used to assess the prognostic values of MKRN3 in terms of overall survival and disease-free survival. The expression differences based on various clinicopathological features were evaluated using subgroup analysis and forest map analysis. The regulatory mechanism of MKRN3 was further investigated using gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses. Subsequently, STRING was used to perform a co-expression and enrichment analysis for MKRN3. Homologous modeling, molecular docking, and western blot analyses were performed to investigate the relationship between MKRN3 and its potential target gene P53. RESULTS: MKRN3 was ectopically expressed between cancerous and noncancerous SCCHN tissues, and its expression level was tightly associated with high T classifications as well as advanced clinical stages. qPCR analysis revealed that MKRN3 was upregulated in the SCCHN cell line. Moreover, Kaplan–Meier and Cox regression analyses indicated that SCCHN patients with high MKRN3 expression had poorer prognosis and that MKRN3 was a potential prognostic marker for SCCHN. Using gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses, we determined that MKRN3 may be involved in the regulation of synthesis and metabolism and cell growth, death and motility, as well as cancer pathways associated with SCCHN progression. Mechanism investigation further revealed that P53, a potential target of MKRN3, may be involved in the SCCHN tumorigenesis mediated by MKRN3. CONCLUSIONS: We performed a comprehensive evaluation of the clinical significance of MKRN3 and explored its underlying mechanisms. We concluded that MKRN3 represents a valuable predictive biomarker and potential therapeutic target in SCCHN. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12935-021-02271-6. |
format | Online Article Text |
id | pubmed-8543891 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-85438912021-10-25 Elevated expression of MKRN3 in squamous cell carcinoma of the head and neck and its clinical significance Zhang, Shuiting Liu, Chao Li, Guo Liu, Yong Wang, Xingwei Qiu, Yuanzheng Cancer Cell Int Primary Research BACKGROUND: Squamous cell carcinoma of the head and neck (SCCHN) is one of the most common types of cancer that cause a substantial number of cancer-related deaths. Our previous study has revealed that makorin ring finger protein 3 (MKRN3) may act as a key regulator of the SCCHN tumorigenesis; however, its specific role in SCCHN progression has not been reported. METHODS: The Cancer Genome Atlas (TCGA) data analysis and quantitative polymerase chain reaction (qPCR) were used to quantify the MKRN3 mRNA expression levels in SCCHN; immunohistochemical staining or immunoblotting analyses were performed to detect MKRN3 protein expression. Kaplan–Meier plotter was used to assess the prognostic values of MKRN3 in terms of overall survival and disease-free survival. The expression differences based on various clinicopathological features were evaluated using subgroup analysis and forest map analysis. The regulatory mechanism of MKRN3 was further investigated using gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses. Subsequently, STRING was used to perform a co-expression and enrichment analysis for MKRN3. Homologous modeling, molecular docking, and western blot analyses were performed to investigate the relationship between MKRN3 and its potential target gene P53. RESULTS: MKRN3 was ectopically expressed between cancerous and noncancerous SCCHN tissues, and its expression level was tightly associated with high T classifications as well as advanced clinical stages. qPCR analysis revealed that MKRN3 was upregulated in the SCCHN cell line. Moreover, Kaplan–Meier and Cox regression analyses indicated that SCCHN patients with high MKRN3 expression had poorer prognosis and that MKRN3 was a potential prognostic marker for SCCHN. Using gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses, we determined that MKRN3 may be involved in the regulation of synthesis and metabolism and cell growth, death and motility, as well as cancer pathways associated with SCCHN progression. Mechanism investigation further revealed that P53, a potential target of MKRN3, may be involved in the SCCHN tumorigenesis mediated by MKRN3. CONCLUSIONS: We performed a comprehensive evaluation of the clinical significance of MKRN3 and explored its underlying mechanisms. We concluded that MKRN3 represents a valuable predictive biomarker and potential therapeutic target in SCCHN. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12935-021-02271-6. BioMed Central 2021-10-24 /pmc/articles/PMC8543891/ /pubmed/34689784 http://dx.doi.org/10.1186/s12935-021-02271-6 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Primary Research Zhang, Shuiting Liu, Chao Li, Guo Liu, Yong Wang, Xingwei Qiu, Yuanzheng Elevated expression of MKRN3 in squamous cell carcinoma of the head and neck and its clinical significance |
title | Elevated expression of MKRN3 in squamous cell carcinoma of the head and neck and its clinical significance |
title_full | Elevated expression of MKRN3 in squamous cell carcinoma of the head and neck and its clinical significance |
title_fullStr | Elevated expression of MKRN3 in squamous cell carcinoma of the head and neck and its clinical significance |
title_full_unstemmed | Elevated expression of MKRN3 in squamous cell carcinoma of the head and neck and its clinical significance |
title_short | Elevated expression of MKRN3 in squamous cell carcinoma of the head and neck and its clinical significance |
title_sort | elevated expression of mkrn3 in squamous cell carcinoma of the head and neck and its clinical significance |
topic | Primary Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8543891/ https://www.ncbi.nlm.nih.gov/pubmed/34689784 http://dx.doi.org/10.1186/s12935-021-02271-6 |
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