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Updated: Aug 20, 2026
Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer
Published on: September 18, 2020
IGSF4 promoter methylation and expression silencing in human cervical cancer
Jianduan Li1, Zhengyan Zhang, Miri Bidder
1Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Objectives:
Functional assays of tumor suppression and loss of heterozygosity point to a tumor suppressor gene (TSG) for cervical cancer (CC) on chromosome 11q23. We evaluated IGSF4, a putative TSG located in the region, for promoter methylation and gene silencing in CC cell lines and cervical tissues.
Methods:
IGSF4 expression was detected by both RT-PCR and Northern blot analysis. Methylation maps of the IGSF4 promoter region were generated for 11 CC cell lines based upon bisulfite-genomic sequencing, using seven nested-PCR primer sets covering 97 CpG sites. Methylation fingerprints in primary cervical tissues were evaluated by denaturing high performance liquid chromatography.
Results:
A 4.4-kb mRNA was seen in cell lines, consistent with the RT-PCR results for both cell lines and primary cervical tissue. IGSF4 was expressed in 6/11 cell lines, 6/8 CC tissues and in all seven normal cervical epithelia. In the cell lines, IGSF4 silencing was associated with promoter hypermethylation. The methylation status in the region covering the -18 to -2 CpG sites correlated most strongly with expression, pointing to the existence of an unmethylated core in the IGSF4 promoter in cell lines expressing IGSF4. This unmethylated core spans approximately 180 bp and is immediately upstream of the ATG site. In primary tissues, methylation was detected in 15/23 (65%) CC specimens but in none of seven normal cervical epithelia.
Conclusions:
Our data strongly suggest that IGSF4 is a TSG and that gene silencing by aberrant hypermethylation may contribute to the development of CC.
Insights
IGSF4, a potential tumor suppressor gene, is silenced by promoter hypermethylation in cervical cancer (CC). This epigenetic silencing may contribute to CC development, highlighting IGSF4 as a target for future therapies.
Area of Science:
- Oncology
- Epigenetics
- Molecular Biology
Background:
- Functional assays suggest a tumor suppressor gene (TSG) on chromosome 11q23 is involved in cervical cancer (CC).
- IGSF4, located in this critical region, was investigated as a potential TSG.
Purpose of the Study:
- To evaluate IGSF4 for promoter methylation and gene silencing in CC cell lines and tissues.
- To determine if IGSF4 acts as a TSG in cervical cancer development.
Main Methods:
- IGSF4 gene expression was analyzed using RT-PCR and Northern blot.
- Bisulfite-genomic sequencing and denaturing high performance liquid chromatography were used to assess promoter methylation in CC cell lines and primary tissues.
Main Results:
- IGSF4 expression was detected in cell lines, CC tissues, and normal cervical epithelia, with silencing observed in some cell lines.
- IGSF4 silencing in cell lines correlated with promoter hypermethylation, particularly in a core region upstream of the ATG site.
- Aberrant promoter methylation of IGSF4 was found in 65% of primary CC specimens but not in normal tissues.
Conclusions:
- IGSF4 is strongly suggested to be a tumor suppressor gene in cervical cancer.
- Aberrant hypermethylation leading to IGSF4 gene silencing is a potential mechanism contributing to CC development.
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