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The expression and prognostic value of transporter 1, ATP binding cassette subfamily B member in clear cell renal cell cancer with experimental validation
Transporter associated with antigen processing 1(TAP1) serves as a protein to transport antigenic peptides from the surface of the endoplasmic reticulum to the lumen of the endoplasmic reticulum when the antigens are presented by major histocompatibility complex type I (MHC-I), which has been identi...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9676953/ https://www.ncbi.nlm.nih.gov/pubmed/36419887 http://dx.doi.org/10.3389/fonc.2022.1013790 |
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author | Wang, Zhen-Da Tian, Xi Wang, Yue Wang, Jun-Jie Ye, Shi-Qi Huang, Yong-Qiang Qu, Yuan-Yuan Chang, Kun Shi, Guo-Hai Ye, Ding-Wei Gu, Cheng-Yuan |
author_facet | Wang, Zhen-Da Tian, Xi Wang, Yue Wang, Jun-Jie Ye, Shi-Qi Huang, Yong-Qiang Qu, Yuan-Yuan Chang, Kun Shi, Guo-Hai Ye, Ding-Wei Gu, Cheng-Yuan |
author_sort | Wang, Zhen-Da |
collection | PubMed |
description | Transporter associated with antigen processing 1(TAP1) serves as a protein to transport antigenic peptides from the surface of the endoplasmic reticulum to the lumen of the endoplasmic reticulum when the antigens are presented by major histocompatibility complex type I (MHC-I), which has been identified to play a critical role in antigen presentation in innate immunity. In tumors, the role of TAP1 seems to remain controversial. On the one hand, given the role of TAP1 in antigen presentation, it is indicated that high TAP1 expression corresponds to the emergence of more neoantigens epitopes that facilitate the recognition for phagocytes, T cells and other cells. On the other hand, the genetic ablation of transporter associated with antigen processing (TAP) results in the presentation of new class I-restricted epitopes encoded in house-keeping products. Opposite result has been revealed by studies in other tumors suggest, which implies a more complex function of TAP1. Therefore, it’s significant to clarify the role of TAP1 in clear cell renal cell carcinoma (ccRCC). In this study, we found the elevated expression levels in mRNA and protein of TAP1 in ccRCC tissues, which indicated a relatively worse prognosis. Transwell assay and Scratch assay in vitro demonstrated the promotive role of TAP1 in ccRCC migration as well as a significant role in metastasis. And the increased expression of TAP1 resulted in more immune cells infiltrated in cancer tissues. TAP1 was also demonstrated to be related to immune regulator genes, as gene set enrichment analysis (GSEA) indicated its significant role in immune regulation. The results of CancerSEA indicated the positive association of the high-level TAP1 expression with epithelial–mesenchymal transition (EMT) and the inverse association with Cell Cycle. The effective drugs were also predicted based on TAP1 expression, of which the high level was indeed associated with resistance to multiple drugs, but some effective drugs still identified based on high TAP1 expression. According to the analysis of various databases, the role of TAP1 in ccRCC was explored, especially in relationship of TAP1 with tumor microenvironment. These results indicate that TAP1 can serve as a potential target for treatment of ccRCC. |
format | Online Article Text |
id | pubmed-9676953 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-96769532022-11-22 The expression and prognostic value of transporter 1, ATP binding cassette subfamily B member in clear cell renal cell cancer with experimental validation Wang, Zhen-Da Tian, Xi Wang, Yue Wang, Jun-Jie Ye, Shi-Qi Huang, Yong-Qiang Qu, Yuan-Yuan Chang, Kun Shi, Guo-Hai Ye, Ding-Wei Gu, Cheng-Yuan Front Oncol Oncology Transporter associated with antigen processing 1(TAP1) serves as a protein to transport antigenic peptides from the surface of the endoplasmic reticulum to the lumen of the endoplasmic reticulum when the antigens are presented by major histocompatibility complex type I (MHC-I), which has been identified to play a critical role in antigen presentation in innate immunity. In tumors, the role of TAP1 seems to remain controversial. On the one hand, given the role of TAP1 in antigen presentation, it is indicated that high TAP1 expression corresponds to the emergence of more neoantigens epitopes that facilitate the recognition for phagocytes, T cells and other cells. On the other hand, the genetic ablation of transporter associated with antigen processing (TAP) results in the presentation of new class I-restricted epitopes encoded in house-keeping products. Opposite result has been revealed by studies in other tumors suggest, which implies a more complex function of TAP1. Therefore, it’s significant to clarify the role of TAP1 in clear cell renal cell carcinoma (ccRCC). In this study, we found the elevated expression levels in mRNA and protein of TAP1 in ccRCC tissues, which indicated a relatively worse prognosis. Transwell assay and Scratch assay in vitro demonstrated the promotive role of TAP1 in ccRCC migration as well as a significant role in metastasis. And the increased expression of TAP1 resulted in more immune cells infiltrated in cancer tissues. TAP1 was also demonstrated to be related to immune regulator genes, as gene set enrichment analysis (GSEA) indicated its significant role in immune regulation. The results of CancerSEA indicated the positive association of the high-level TAP1 expression with epithelial–mesenchymal transition (EMT) and the inverse association with Cell Cycle. The effective drugs were also predicted based on TAP1 expression, of which the high level was indeed associated with resistance to multiple drugs, but some effective drugs still identified based on high TAP1 expression. According to the analysis of various databases, the role of TAP1 in ccRCC was explored, especially in relationship of TAP1 with tumor microenvironment. These results indicate that TAP1 can serve as a potential target for treatment of ccRCC. Frontiers Media S.A. 2022-11-07 /pmc/articles/PMC9676953/ /pubmed/36419887 http://dx.doi.org/10.3389/fonc.2022.1013790 Text en Copyright © 2022 Wang, Tian, Wang, Wang, Ye, Huang, Qu, Chang, Shi, Ye and Gu 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 Wang, Zhen-Da Tian, Xi Wang, Yue Wang, Jun-Jie Ye, Shi-Qi Huang, Yong-Qiang Qu, Yuan-Yuan Chang, Kun Shi, Guo-Hai Ye, Ding-Wei Gu, Cheng-Yuan The expression and prognostic value of transporter 1, ATP binding cassette subfamily B member in clear cell renal cell cancer with experimental validation |
title | The expression and prognostic value of transporter 1, ATP binding cassette subfamily B member in clear cell renal cell cancer with experimental validation |
title_full | The expression and prognostic value of transporter 1, ATP binding cassette subfamily B member in clear cell renal cell cancer with experimental validation |
title_fullStr | The expression and prognostic value of transporter 1, ATP binding cassette subfamily B member in clear cell renal cell cancer with experimental validation |
title_full_unstemmed | The expression and prognostic value of transporter 1, ATP binding cassette subfamily B member in clear cell renal cell cancer with experimental validation |
title_short | The expression and prognostic value of transporter 1, ATP binding cassette subfamily B member in clear cell renal cell cancer with experimental validation |
title_sort | expression and prognostic value of transporter 1, atp binding cassette subfamily b member in clear cell renal cell cancer with experimental validation |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9676953/ https://www.ncbi.nlm.nih.gov/pubmed/36419887 http://dx.doi.org/10.3389/fonc.2022.1013790 |
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