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

Kong LM, Liao CG, Chen L, Yang HS, Zhang SH, Zhang Z, Bian HJ, Xing JL, Chen ZN - J. Cell. Mol. Med. (2010)

Bottom Line: 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.Moreover, HCC patients with unmethylated CD147 promoter had a significantly higher recurrence rate (88.1%versus 58.3%; P < 0.05) and death rate (83.3%versus 50.0%; P < 0.05) than patients with methylated CD147 promoter.In conclusions, promoter hypomethylation up-regulates CD147 expression primarily through increasing Sp1 binding and associates with poor prognosis in HCC patients.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Cancer Biology, Cell Engineering Research Centre & Department of Cell Biology, Fourth Military Medical University, Xi'an, China.

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Related in: MedlinePlus

DNA Methylation profile of the CpG island at the CD147 promoter region. (A) Map of predicted CpG islands. One CpG island located at −340 to +37 was identified in CD147 promoter (+1, transcriptional start site; ATG, translational starting site). GC percentage and observed/expected CpG were calculated using the CPGPLOT program. (B) Schematic representation of CpG island. The 46 CG dinucleotides were denoted as grey shadow. CpG sites were numbered from 1 to 46 relative to the transcription start site (+1 indicated with an arrow). Underlined region indicated Sp1 binding sites. (C) Sequences of the CD147 promoter region after bisulphite modification were analysed in normal and cancer cell lines. Black circle, methylated cytosine; white circle, unmethylated cytosine in the dinucleotide CpG.
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fig02: DNA Methylation profile of the CpG island at the CD147 promoter region. (A) Map of predicted CpG islands. One CpG island located at −340 to +37 was identified in CD147 promoter (+1, transcriptional start site; ATG, translational starting site). GC percentage and observed/expected CpG were calculated using the CPGPLOT program. (B) Schematic representation of CpG island. The 46 CG dinucleotides were denoted as grey shadow. CpG sites were numbered from 1 to 46 relative to the transcription start site (+1 indicated with an arrow). Underlined region indicated Sp1 binding sites. (C) Sequences of the CD147 promoter region after bisulphite modification were analysed in normal and cancer cell lines. Black circle, methylated cytosine; white circle, unmethylated cytosine in the dinucleotide CpG.

Mentions: We first analysed the DNA sequence of the CD147 promoter region (NT_011255) defined by Liang L et al. [28] using the CpG Island Searcher program CPGPLOT with the default setting (%GC >55%, ObsCpG/ ExpCpG >0.65) [21]. Our result indicated that one typical CpG island ranging from −340 to +37 existed in CD147 promoter region (Fig. 2A). With the assistance of the TRANSFAC database, four potential binding sites of transcription factor Sp1 were found in the region of −340 to +37. The typical 46 CpG sites located in this region was also indicated in a simplified schematic overview (Fig. 2B). To examine the correlation between DNA methylation and CD147 expression, we further investigated the methylation status of CD147 promoter region in all cell lines and normal liver tissues by BGS. As shown in Figure 2C, all normal cell lines and normal liver tissues exhibited a denser methylation pattern at CD147 promoter region than corresponding HCC cell lines. Further analysis indicated that the methylation levels of four potential Sp1 binding sites (including CpG sites 3, 4, 19, 20, 26, 39 and 40) were also significantly lower in HCC cell lines than in normal cell lines and tissues (Fig. 2C). These findings suggested that the hypomethylation of CD147 promoter region may contribute to the increased CD147 expression in HCC cell lines.


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

Kong LM, Liao CG, Chen L, Yang HS, Zhang SH, Zhang Z, Bian HJ, Xing JL, Chen ZN - J. Cell. Mol. Med. (2010)

DNA Methylation profile of the CpG island at the CD147 promoter region. (A) Map of predicted CpG islands. One CpG island located at −340 to +37 was identified in CD147 promoter (+1, transcriptional start site; ATG, translational starting site). GC percentage and observed/expected CpG were calculated using the CPGPLOT program. (B) Schematic representation of CpG island. The 46 CG dinucleotides were denoted as grey shadow. CpG sites were numbered from 1 to 46 relative to the transcription start site (+1 indicated with an arrow). Underlined region indicated Sp1 binding sites. (C) Sequences of the CD147 promoter region after bisulphite modification were analysed in normal and cancer cell lines. Black circle, methylated cytosine; white circle, unmethylated cytosine in the dinucleotide CpG.
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4373337&req=5

fig02: DNA Methylation profile of the CpG island at the CD147 promoter region. (A) Map of predicted CpG islands. One CpG island located at −340 to +37 was identified in CD147 promoter (+1, transcriptional start site; ATG, translational starting site). GC percentage and observed/expected CpG were calculated using the CPGPLOT program. (B) Schematic representation of CpG island. The 46 CG dinucleotides were denoted as grey shadow. CpG sites were numbered from 1 to 46 relative to the transcription start site (+1 indicated with an arrow). Underlined region indicated Sp1 binding sites. (C) Sequences of the CD147 promoter region after bisulphite modification were analysed in normal and cancer cell lines. Black circle, methylated cytosine; white circle, unmethylated cytosine in the dinucleotide CpG.
Mentions: We first analysed the DNA sequence of the CD147 promoter region (NT_011255) defined by Liang L et al. [28] using the CpG Island Searcher program CPGPLOT with the default setting (%GC >55%, ObsCpG/ ExpCpG >0.65) [21]. Our result indicated that one typical CpG island ranging from −340 to +37 existed in CD147 promoter region (Fig. 2A). With the assistance of the TRANSFAC database, four potential binding sites of transcription factor Sp1 were found in the region of −340 to +37. The typical 46 CpG sites located in this region was also indicated in a simplified schematic overview (Fig. 2B). To examine the correlation between DNA methylation and CD147 expression, we further investigated the methylation status of CD147 promoter region in all cell lines and normal liver tissues by BGS. As shown in Figure 2C, all normal cell lines and normal liver tissues exhibited a denser methylation pattern at CD147 promoter region than corresponding HCC cell lines. Further analysis indicated that the methylation levels of four potential Sp1 binding sites (including CpG sites 3, 4, 19, 20, 26, 39 and 40) were also significantly lower in HCC cell lines than in normal cell lines and tissues (Fig. 2C). These findings suggested that the hypomethylation of CD147 promoter region may contribute to the increased CD147 expression in HCC cell lines.

Bottom Line: 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.Moreover, HCC patients with unmethylated CD147 promoter had a significantly higher recurrence rate (88.1%versus 58.3%; P < 0.05) and death rate (83.3%versus 50.0%; P < 0.05) than patients with methylated CD147 promoter.In conclusions, promoter hypomethylation up-regulates CD147 expression primarily through increasing Sp1 binding and associates with poor prognosis in HCC patients.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Cancer Biology, Cell Engineering Research Centre & Department of Cell Biology, Fourth Military Medical University, Xi'an, China.

Show MeSH
Related in: MedlinePlus