DNA methylation and carcinogenesis of PRDM5 in cervical cancer.
OBJECTIVE
PR (PRDI-BF1 and RIZ) domain proteins (PRDM) are a subfamily of the kruppel-like zinc finger gene products and play key roles during cell differentiation and malignant transformation. PRDM5 (PR domain containing 5 PFM2) is a new PR-domain-containing gene. The purpose of the present study was to examine the expression of PRDM5 and evaluate its carcinogenesis in cervical cancer. The relationship between DNA methylation and transcriptional silencing of PRDM5 was investigated in cervical cancer.


METHODS
PRDM5 expression was examined in cervical cancer cell lines and cervical tissues (12 normal and 42 cancerous) by using RT polymerase chain reaction (PCR). Methylation status of the PRDM5 promoter was studied using methylation-specific PCR (MSP).


RESULTS
PRDM5 expression is reduced or lost in cervical cancers, compared with normal cervical tissues (P < 0.05). The current study results also showed that loss of PRDM5 is mediated by aberrant cytosine methylation of the PRDM5 promoter. There were 40.5% of carcinomas methylated, while none of normal tissues were methylated. PRDM5 mRNA expression was significantly higher (P = 0.000) in unmethylated (0.2634 ± 0.0674, mean ± SD), compared with methylated tissues (0.1007 ± 0.0993, mean ± SD). Last, treatment with a DNA methyltransferase inhibitor led to reactivation of PRDM5 expression in cell lines that had negligible PRDM5 expression at baseline.


CONCLUSIONS
Reduced expression of PRDM5 may play an important role in the pathogenesis and/or development of cervical cancer, and is considered to be caused in part by aberrant DNA methylation.
Cheng
Hai-Yan
HY
Department of Gynecologic Oncology, The Tumor Hospital of Harbin Medical University, 150 Haping Road, Heilongjiang 150081, China.
Chen
Xiu-Wei
XW
Cheng
Li
L
Liu
Yun-Duo
YD
Lou
Ge
G
D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D045744:Cell Line, Tumor; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000037:antagonists & inhibitors; D004268:DNA-Binding Proteins / Q000235:genetics*; D000077209:Decitabine; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D020022:Genetic Predisposition to Disease; D006367:HeLa Cells; D006801:Humans; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics*; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology
D004268:DNA-Binding Proteins; C487762:PRDM5 protein, human; D012333:RNA, Messenger; D014157:Transcription Factors; D000077209:Decitabine; D015254:DNA Modification Methylases; D001374:Azacitidine