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Post-Transcriptional and Epigenetic Regulation of Antigen Processing Machinery (APM) Components and HLA-I in Cervical Cancers from Uighur Women

Normal function of human leukocyte antigen class I (HLA-I) and antigen processing machinery (APM) proteins is required for T cell-mediated anti-tumor or antiviral immunity, whereas the tumor survival indicates a failure of the host in immune surveillance associated with the dysfunction in antigen pr...

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Autores principales: Hasim, Ayshamgul, Abudula, Mangnishahan, Aimiduo, Reshalaiti, Ma, Jun-Qi, Jiao, Zhen, Akula, Gulzareye, Wang, Ting, Abudula, Abulizi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3443204/
https://www.ncbi.nlm.nih.gov/pubmed/23024775
http://dx.doi.org/10.1371/journal.pone.0044952
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author Hasim, Ayshamgul
Abudula, Mangnishahan
Aimiduo, Reshalaiti
Ma, Jun-Qi
Jiao, Zhen
Akula, Gulzareye
Wang, Ting
Abudula, Abulizi
author_facet Hasim, Ayshamgul
Abudula, Mangnishahan
Aimiduo, Reshalaiti
Ma, Jun-Qi
Jiao, Zhen
Akula, Gulzareye
Wang, Ting
Abudula, Abulizi
author_sort Hasim, Ayshamgul
collection PubMed
description Normal function of human leukocyte antigen class I (HLA-I) and antigen processing machinery (APM) proteins is required for T cell-mediated anti-tumor or antiviral immunity, whereas the tumor survival indicates a failure of the host in immune surveillance associated with the dysfunction in antigen presentation, mainly due to the deregulation in HLA-I and APM expression or function. The posttranscriptional regulation of HLA-I and APM expression may associate with epigenetic modifications in cancer development which was not described so far. Here we showed that the development of cervical intraepithelial neoplasia (CIN) and cervical squamous cell carcinoma (CSCC) in Uighur women was accompanied with the partial or total loss of protein expression of HLA-I, ß2-m and APM components, including the transporter associated with antigen processing (TAP1/2), low molecular mass protein (LMP2, LMP7), endoplasmic reticulum aminopeptidase 1(ERAP1), chaperone molecules include calreticulin (CLR), calnexin (CNX) and ERp57, and this was proved again by analysis of transcription of the same genes in addition to three genes HLA-A, B and C coding for HLA-I. By bisulfite sequencing approach, we identified target CpG islands methylated at the gene promoter region of TAP1, TAP2, LMP7, tapasin and ERp57 in cervical carcinoma cells. Further analysis of CpG site specific methylation of these genes in cases of CSCC and CIN demonstrated an inverse correlation of altered CpG island methylation of TAP1, LMP7, and ERp57 with changes in protein expression. Moreover, promoter methylation of these genes was significantly higher in cases positive for human papillomavirus 16 (HPV 16) than negative ones. Our results suggested that epigenetic modifications are responsible for the aberrant expression of certain HLA-I and APM genes, and may help to understand unrevealed mechanisms of tumor escape from immune surveillance in cervical carcinogenesis.
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spelling pubmed-34432042012-09-28 Post-Transcriptional and Epigenetic Regulation of Antigen Processing Machinery (APM) Components and HLA-I in Cervical Cancers from Uighur Women Hasim, Ayshamgul Abudula, Mangnishahan Aimiduo, Reshalaiti Ma, Jun-Qi Jiao, Zhen Akula, Gulzareye Wang, Ting Abudula, Abulizi PLoS One Research Article Normal function of human leukocyte antigen class I (HLA-I) and antigen processing machinery (APM) proteins is required for T cell-mediated anti-tumor or antiviral immunity, whereas the tumor survival indicates a failure of the host in immune surveillance associated with the dysfunction in antigen presentation, mainly due to the deregulation in HLA-I and APM expression or function. The posttranscriptional regulation of HLA-I and APM expression may associate with epigenetic modifications in cancer development which was not described so far. Here we showed that the development of cervical intraepithelial neoplasia (CIN) and cervical squamous cell carcinoma (CSCC) in Uighur women was accompanied with the partial or total loss of protein expression of HLA-I, ß2-m and APM components, including the transporter associated with antigen processing (TAP1/2), low molecular mass protein (LMP2, LMP7), endoplasmic reticulum aminopeptidase 1(ERAP1), chaperone molecules include calreticulin (CLR), calnexin (CNX) and ERp57, and this was proved again by analysis of transcription of the same genes in addition to three genes HLA-A, B and C coding for HLA-I. By bisulfite sequencing approach, we identified target CpG islands methylated at the gene promoter region of TAP1, TAP2, LMP7, tapasin and ERp57 in cervical carcinoma cells. Further analysis of CpG site specific methylation of these genes in cases of CSCC and CIN demonstrated an inverse correlation of altered CpG island methylation of TAP1, LMP7, and ERp57 with changes in protein expression. Moreover, promoter methylation of these genes was significantly higher in cases positive for human papillomavirus 16 (HPV 16) than negative ones. Our results suggested that epigenetic modifications are responsible for the aberrant expression of certain HLA-I and APM genes, and may help to understand unrevealed mechanisms of tumor escape from immune surveillance in cervical carcinogenesis. Public Library of Science 2012-09-14 /pmc/articles/PMC3443204/ /pubmed/23024775 http://dx.doi.org/10.1371/journal.pone.0044952 Text en © 2012 Hasim et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Hasim, Ayshamgul
Abudula, Mangnishahan
Aimiduo, Reshalaiti
Ma, Jun-Qi
Jiao, Zhen
Akula, Gulzareye
Wang, Ting
Abudula, Abulizi
Post-Transcriptional and Epigenetic Regulation of Antigen Processing Machinery (APM) Components and HLA-I in Cervical Cancers from Uighur Women
title Post-Transcriptional and Epigenetic Regulation of Antigen Processing Machinery (APM) Components and HLA-I in Cervical Cancers from Uighur Women
title_full Post-Transcriptional and Epigenetic Regulation of Antigen Processing Machinery (APM) Components and HLA-I in Cervical Cancers from Uighur Women
title_fullStr Post-Transcriptional and Epigenetic Regulation of Antigen Processing Machinery (APM) Components and HLA-I in Cervical Cancers from Uighur Women
title_full_unstemmed Post-Transcriptional and Epigenetic Regulation of Antigen Processing Machinery (APM) Components and HLA-I in Cervical Cancers from Uighur Women
title_short Post-Transcriptional and Epigenetic Regulation of Antigen Processing Machinery (APM) Components and HLA-I in Cervical Cancers from Uighur Women
title_sort post-transcriptional and epigenetic regulation of antigen processing machinery (apm) components and hla-i in cervical cancers from uighur women
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3443204/
https://www.ncbi.nlm.nih.gov/pubmed/23024775
http://dx.doi.org/10.1371/journal.pone.0044952
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