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

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 (<i>n</i> = 162) and without rad...

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Autores principales:	Ting-Wen Chen, Kai-Ping Chang, Chun-Chia Cheng, Cheng-Yi Chen, Shu-Wen Hong, Zong-Lin Sie, Hsing-Wen Cheng, Wei-Chen Yen, Yenlin Huang, Shu-Chen Liu, Chun-I Wang
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	oral cancer oral cavity squamous cell carcinoma OSCC radioresistance RPL36A radiotherapy Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/182609c5a290455ca2ec0790ad0c4031
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spelling	oai:doaj.org-article:182609c5a290455ca2ec0790ad0c40312021-11-25T17:01:44ZCharacterization of Recurrent Relevant Genes Reveals a Novel Role of RPL36A in Radioresistant Oral Squamous Cell Carcinoma10.3390/cancers132256232072-6694https://doaj.org/article/182609c5a290455ca2ec0790ad0c40312021-11-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/22/5623https://doaj.org/toc/2072-6694Radioresistance 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 (<i>n</i> = 162) and without radiotherapy (<i>n</i> = 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 (<i>n</i> = 162 and <i>n</i> = 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.Ting-Wen ChenKai-Ping ChangChun-Chia ChengCheng-Yi ChenShu-Wen HongZong-Lin SieHsing-Wen ChengWei-Chen YenYenlin HuangShu-Chen LiuChun-I WangMDPI AGarticleoral canceroral cavity squamous cell carcinomaOSCCradioresistanceRPL36AradiotherapyNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5623, p 5623 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	oral cancer oral cavity squamous cell carcinoma OSCC radioresistance RPL36A radiotherapy Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	oral cancer oral cavity squamous cell carcinoma OSCC radioresistance RPL36A radiotherapy Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Ting-Wen Chen Kai-Ping Chang Chun-Chia Cheng Cheng-Yi Chen Shu-Wen Hong Zong-Lin Sie Hsing-Wen Cheng Wei-Chen Yen Yenlin Huang Shu-Chen Liu Chun-I Wang Characterization of Recurrent Relevant Genes Reveals a Novel Role of RPL36A in Radioresistant Oral Squamous Cell Carcinoma
description	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 (<i>n</i> = 162) and without radiotherapy (<i>n</i> = 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 (<i>n</i> = 162 and <i>n</i> = 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.
format	article
author	Ting-Wen Chen Kai-Ping Chang Chun-Chia Cheng Cheng-Yi Chen Shu-Wen Hong Zong-Lin Sie Hsing-Wen Cheng Wei-Chen Yen Yenlin Huang Shu-Chen Liu Chun-I Wang
author_facet	Ting-Wen Chen Kai-Ping Chang Chun-Chia Cheng Cheng-Yi Chen Shu-Wen Hong Zong-Lin Sie Hsing-Wen Cheng Wei-Chen Yen Yenlin Huang Shu-Chen Liu Chun-I Wang
author_sort	Ting-Wen Chen
title	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_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_sort	characterization of recurrent relevant genes reveals a novel role of rpl36a in radioresistant oral squamous cell carcinoma
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/182609c5a290455ca2ec0790ad0c4031
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Characterization of Recurrent Relevant Genes Reveals a Novel Role of RPL36A in Radioresistant Oral Squamous Cell Carcinoma

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