Post-transcriptional and epigenetic regulation of antigen processing machinery (APM) components and HLA-I in cervical cancers from Uighur women

Autor: Jun-qi Ma, Ting Wang, Zhen Jiao, Gulzareye Akula, Reshalaiti Aimiduo, Mangnishahan Abudula, Ayshamgul Hasim, Abulizi Abudula
Rok vydání: 2012
Předmět:
Viral Diseases
Bisulfite sequencing
lcsh:Medicine
Uterine Cervical Neoplasms
Cervical Cancer
Epigenesis
Genetic
RNA Processing
Post-Transcriptional
lcsh:Science
Promoter Regions
Genetic
Immune Response
Regulation of gene expression
Antigen Presentation
Multidisciplinary
biology
Antigen processing
Obstetrics and Gynecology
Transporter associated with antigen processing
Middle Aged
Gene Expression Regulation
Neoplastic
Infectious Diseases
Oncology
DNA methylation
Carcinoma
Squamous Cell
Medicine
Female
Research Article
Adult
China
Human Papillomavirus Infection
Urology
Sexually Transmitted Diseases
Asian People
Cell Line
Tumor
Humans
Epigenetics
RNA
Messenger
Aged
Neoplasm Staging
Genitourinary Infections
lcsh:R
Histocompatibility Antigens Class I
Papillomavirus Infections
Cancers and Neoplasms
DNA Methylation
biology.protein
Cancer research
lcsh:Q
CpG Islands
Clinical Immunology
TAP1
Calreticulin
Gynecological Tumors
Zdroj: PLoS ONE
PLoS ONE, Vol 7, Iss 9, p e44952 (2012)
ISSN: 1932-6203
Popis: 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.
Databáze: OpenAIRE
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