PMID- 23024775
OWN - NLM
STAT- MEDLINE
DCOM- 20130215
LR  - 20221207
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 7
IP  - 9
DP  - 2012
TI  - Post-transcriptional and epigenetic regulation of antigen processing machinery 
      (APM) components and HLA-I in cervical cancers from Uighur women.
PG  - e44952
LID - e44952
AB  - 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.
FAU - Hasim, Ayshamgul
AU  - Hasim A
AD  - Department of Pathology, College of Basic Medicine, Medical University of 
      Xinjiang, Urumqi, People's Republic of China.
FAU - Abudula, Mangnishahan
AU  - Abudula M
FAU - Aimiduo, Reshalaiti
AU  - Aimiduo R
FAU - Ma, Jun-Qi
AU  - Ma JQ
FAU - Jiao, Zhen
AU  - Jiao Z
FAU - Akula, Gulzareye
AU  - Akula G
FAU - Wang, Ting
AU  - Wang T
FAU - Abudula, Abulizi
AU  - Abudula A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120914
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (RNA, Messenger)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antigen Presentation/*genetics
MH  - Asian People/genetics
MH  - Carcinoma, Squamous Cell/genetics/immunology/pathology/virology
MH  - Cell Line, Tumor
MH  - China
MH  - CpG Islands
MH  - DNA Methylation
MH  - *Epigenesis, Genetic
MH  - Female
MH  - Gene Expression Regulation, Neoplastic
MH  - Histocompatibility Antigens Class I/*genetics/immunology
MH  - Humans
MH  - Middle Aged
MH  - Neoplasm Staging
MH  - Papillomavirus Infections
MH  - Promoter Regions, Genetic
MH  - *RNA Processing, Post-Transcriptional
MH  - RNA, Messenger
MH  - Uterine Cervical Neoplasms/*genetics/immunology/pathology/virology
PMC - PMC3443204
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2012/10/02 06:00
MHDA- 2013/02/16 06:00
PMCR- 2012/09/14
CRDT- 2012/10/02 06:00
PHST- 2012/01/20 00:00 [received]
PHST- 2012/08/14 00:00 [accepted]
PHST- 2012/10/02 06:00 [entrez]
PHST- 2012/10/02 06:00 [pubmed]
PHST- 2013/02/16 06:00 [medline]
PHST- 2012/09/14 00:00 [pmc-release]
AID - PONE-D-12-02129 [pii]
AID - 10.1371/journal.pone.0044952 [doi]
PST - ppublish
SO  - PLoS One. 2012;7(9):e44952. doi: 10.1371/journal.pone.0044952. Epub 2012 Sep 14.