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Characterization of Recurrent Relevant Genes Reveals a Novel Role of RPL36A in Radioresistant Oral Squamous Cell Carcinoma

SIMPLE SUMMARY: Radioresistance is one of the major factors contributing to radiotherapy failure in OSCC. By systematically comparing the prognostic values of all genes in TCGA-OSCC patients with and without radiotherapy, radioresistance-associated genes were identified. Higher RPL36A transcript lev...

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Autores principales: Chen, Ting-Wen, Chang, Kai-Ping, Cheng, Chun-Chia, Chen, Cheng-Yi, Hong, Shu-Wen, Sie, Zong-Lin, Cheng, Hsing-Wen, Yen, Wei-Chen, Huang, Yenlin, Liu, Shu-Chen, Wang, Chun-I
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8616119/
https://www.ncbi.nlm.nih.gov/pubmed/34830778
http://dx.doi.org/10.3390/cancers13225623
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author Chen, Ting-Wen
Chang, Kai-Ping
Cheng, Chun-Chia
Chen, Cheng-Yi
Hong, Shu-Wen
Sie, Zong-Lin
Cheng, Hsing-Wen
Yen, Wei-Chen
Huang, Yenlin
Liu, Shu-Chen
Wang, Chun-I
author_facet Chen, Ting-Wen
Chang, Kai-Ping
Cheng, Chun-Chia
Chen, Cheng-Yi
Hong, Shu-Wen
Sie, Zong-Lin
Cheng, Hsing-Wen
Yen, Wei-Chen
Huang, Yenlin
Liu, Shu-Chen
Wang, Chun-I
author_sort Chen, Ting-Wen
collection PubMed
description SIMPLE SUMMARY: Radioresistance is one of the major factors contributing to radiotherapy failure in OSCC. By systematically comparing the prognostic values of all genes in TCGA-OSCC patients with and without radiotherapy, radioresistance-associated genes were identified. Higher RPL36A transcript levels were found to be associated with a poor prognosis only in OSCC patients with radiotherapy in the cohort of TCGA and another independent Taiwanese cohort. RPL36A was then shown to be involved in the regulation of DNA damage, cell cycle and apoptosis, leading to radioresistance. Thus, such integrated studies are expected to be greatly beneficial for the development of new therapeutic interventions for radioresistant OSCC in the future. ABSTRACT: Radioresistance is one of the major factors that contributes to radiotherapy failure in oral cavity squamous cell carcinoma (OSCC). By comparing the prognostic values of 20,502 genes expressed in patients in The Cancer Genome Atlas (TCGA)-OSCC cohort with (n = 162) and without radiotherapy (n = 118), herein identified 297 genes positively correlated with poor disease-free survival in OSCC patients with radiotherapy as the potential radioresistance-associated genes. Among the potential radioresistance-associated genes, 36 genes were upregulated in cancerous tissues relative to normal tissues. The bioinformatics analysis revealed that 60S ribosomal protein L36a (RPL36A) was the most frequently detected gene involved in radioresistance-associated gene-mediated biological pathways. Then, two independent cohorts (n = 162 and n = 136) were assessed to confirm that higher RPL36A transcript levels were significantly associated with a poor prognosis only in OSCC patients with radiotherapy. Mechanistically, we found that knockdown of RPL36A increased radiosensitivity via sensitizing cells to DNA damage and promoted G2/M cell cycle arrest followed by augmenting the irradiation-induced apoptosis pathway in OSCC cells. Taken together, our study supports the use of large-scale genomic data for identifying specific radioresistance-associated genes and suggests a regulatory role for RPL36A in the development of radioresistance in OSCC.
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spelling pubmed-86161192021-11-26 Characterization of Recurrent Relevant Genes Reveals a Novel Role of RPL36A in Radioresistant Oral Squamous Cell Carcinoma Chen, Ting-Wen Chang, Kai-Ping Cheng, Chun-Chia Chen, Cheng-Yi Hong, Shu-Wen Sie, Zong-Lin Cheng, Hsing-Wen Yen, Wei-Chen Huang, Yenlin Liu, Shu-Chen Wang, Chun-I Cancers (Basel) Article SIMPLE SUMMARY: Radioresistance is one of the major factors contributing to radiotherapy failure in OSCC. By systematically comparing the prognostic values of all genes in TCGA-OSCC patients with and without radiotherapy, radioresistance-associated genes were identified. Higher RPL36A transcript levels were found to be associated with a poor prognosis only in OSCC patients with radiotherapy in the cohort of TCGA and another independent Taiwanese cohort. RPL36A was then shown to be involved in the regulation of DNA damage, cell cycle and apoptosis, leading to radioresistance. Thus, such integrated studies are expected to be greatly beneficial for the development of new therapeutic interventions for radioresistant OSCC in the future. ABSTRACT: Radioresistance is one of the major factors that contributes to radiotherapy failure in oral cavity squamous cell carcinoma (OSCC). By comparing the prognostic values of 20,502 genes expressed in patients in The Cancer Genome Atlas (TCGA)-OSCC cohort with (n = 162) and without radiotherapy (n = 118), herein identified 297 genes positively correlated with poor disease-free survival in OSCC patients with radiotherapy as the potential radioresistance-associated genes. Among the potential radioresistance-associated genes, 36 genes were upregulated in cancerous tissues relative to normal tissues. The bioinformatics analysis revealed that 60S ribosomal protein L36a (RPL36A) was the most frequently detected gene involved in radioresistance-associated gene-mediated biological pathways. Then, two independent cohorts (n = 162 and n = 136) were assessed to confirm that higher RPL36A transcript levels were significantly associated with a poor prognosis only in OSCC patients with radiotherapy. Mechanistically, we found that knockdown of RPL36A increased radiosensitivity via sensitizing cells to DNA damage and promoted G2/M cell cycle arrest followed by augmenting the irradiation-induced apoptosis pathway in OSCC cells. Taken together, our study supports the use of large-scale genomic data for identifying specific radioresistance-associated genes and suggests a regulatory role for RPL36A in the development of radioresistance in OSCC. MDPI 2021-11-10 /pmc/articles/PMC8616119/ /pubmed/34830778 http://dx.doi.org/10.3390/cancers13225623 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Chen, Ting-Wen
Chang, Kai-Ping
Cheng, Chun-Chia
Chen, Cheng-Yi
Hong, Shu-Wen
Sie, Zong-Lin
Cheng, Hsing-Wen
Yen, Wei-Chen
Huang, Yenlin
Liu, Shu-Chen
Wang, Chun-I
Characterization of Recurrent Relevant Genes Reveals a Novel Role of RPL36A in Radioresistant Oral Squamous Cell Carcinoma
title Characterization of Recurrent Relevant Genes Reveals a Novel Role of RPL36A in Radioresistant Oral Squamous Cell Carcinoma
title_full Characterization of Recurrent Relevant Genes Reveals a Novel Role of RPL36A in Radioresistant Oral Squamous Cell Carcinoma
title_fullStr Characterization of Recurrent Relevant Genes Reveals a Novel Role of RPL36A in Radioresistant Oral Squamous Cell Carcinoma
title_full_unstemmed Characterization of Recurrent Relevant Genes Reveals a Novel Role of RPL36A in Radioresistant Oral Squamous Cell Carcinoma
title_short Characterization of Recurrent Relevant Genes Reveals a Novel Role of RPL36A in Radioresistant Oral Squamous Cell Carcinoma
title_sort characterization of recurrent relevant genes reveals a novel role of rpl36a in radioresistant oral squamous cell carcinoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8616119/
https://www.ncbi.nlm.nih.gov/pubmed/34830778
http://dx.doi.org/10.3390/cancers13225623
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