Promoter hypomethylation up-regulates CD147 expression through increasing Sp1 binding and associates with poor prognosis in human hepatocellular carcinoma.

Journal of Cellular and Molecular Medicine
Ling-Min KongZhi-Nan Chen

Abstract

CD147 is a transmembrane glycoprotein overexpressed in human hepatocellular carcinoma (HCC) which could promote HCC progression and metastasis. Promoter methylation is one of the most important processes in gene regulation. In this study, we aim to investigate CD147 promoter methylation status and the correlation with clinicopathological features and prognosis in HCC. CD147 promoter methylation statuses and expression levels in normal and HCC cell lines and 54 paired HCC and adjacent non-tumour (ANT) tissues were, respectively, examined by bisulphite genomic sequencing, methylation-specific PCR, real-time RT-PCR, Western blot and immunohistochemistry. The correlations of promoter methylation statuses with CD147 expression level and the clinicopathological features were statistically analysed in HCC patients. Significantly higher expression of CD147 and significantly lower promoter methylation level were observed in HCC cell lines compared to normal cell lines and tissues control. In vivo and in vitro analysis indicated that demethylation with 5-Aza-2'-deoxycytidine led to increased CD147 expression through enhancing Sp1 binding affinity, and methylation with methyltransferase reduced CD147 transcriptional activity through inter...Continue Reading

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Citations

Aug 31, 2012·Journal of Drug Targeting·Xu TangMan Mi
Sep 11, 2014·Pharmacology & Therapeutics·Ioannis AnestopoulosMihalis I Panayiotidis
May 11, 2012·International Journal of Cancer. Journal International Du Cancer·Jing HuangLonghua Chen
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Dec 29, 2016·The Journal of Biological Chemistry·Qiaojiajie ZhaoDeng Chen
Dec 14, 2018·International Journal of Molecular Sciences·Tae-Su HanHyun-Soo Cho

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Methods Mentioned

BETA
surgical resections
PCR
transfection
immunoprecipitation
Gel Shift
ChIP
electrophoretic mobility shift

Software Mentioned

CPGPLOT
Opticon Monitor
SPSS

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