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Updated: May 3, 2026
miRNA Expression Analyses in Prostate Cancer Clinical Tissues
Published on: September 8, 2015
Hypermethylation of miR-203 in endometrial carcinomas
Yi-Wen Huang1, Chieh-Ti Kuo2, Jo-Hsin Chen2
1Department of Obstetrics and Gynecology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Objectives:
Aberrant expression of SOX4 in endometrial cancer has been identified and partially was contributed to hypermethylation of miR-129-2. Other miRNAs are suspected to influence SOX 4 as well. The current study seeks to identify other hypermethylated miRNAs that regulate SOX4 in endometrial carcinomas.
Methods:
Methylation levels of miRNA promoter regions were measured by combined bisulfite restriction analysis (COBRA) and pyrosequencing assays. Gene expression was determined by RT-qPCR. Methylation level of a miRNA locus was corrected with clinicopathologic factors for 252 gynecological specimens.
Results:
In silico analysis identified 13 miRNA loci bound on the 3'-UTR of SOX4. Using COBRA assays, increased methylation of miR-203, miR-219-2, miR-596, and miR-618 was detected in endometrial cancer cells relative to those seen in a normal cell line and in normal endometrium. Transfection of a miR-203 mimic decreased SOX4 gene expression. Hypermethylation of miR-203 was detected in 52% of type I endometrioid endometrial carcinomas (n=131) but was not seen in any of 10 uninvolved normal endometria (P<0.001). Methylation status of miR-203 was significantly associated with microsatellite instability and MLH1 methylation in endometrial tumors (P<0.001). Furthermore, hypermethylation of miR-203 was found in endometrioid and clear endometrial subtype tumors, but not in cervical squamous cell and ovarian carcinomas.
Conclusions:
Hypermethylation of miR-203 is a frequent event in endometrial carcinomas and is strongly associated with microsatellite instability and MLH1 methylation status. Thus, miR-203 methylation level might represent a marker for patients with endometrioid and clear endometrial sub-cancers.
Insights
Hypermethylation of miR-203 frequently occurs in endometrial cancer, impacting SOX4 expression. This methylation may serve as a biomarker for specific endometrial cancer subtypes, particularly endometrioid and clear cell carcinomas.
Area of Science:
- Oncology
- Molecular Biology
- Epigenetics
Background:
- Aberrant SOX4 expression is implicated in endometrial cancer.
- Hypermethylation of miR-129-2 is a known contributor to SOX4 dysregulation.
- Other microRNAs (miRNAs) are suspected to regulate SOX4 in endometrial carcinomas.
Purpose of the Study:
- To identify additional hypermethylated miRNAs that target and regulate SOX4 in endometrial carcinomas.
- To investigate the role of miRNA promoter methylation in endometrial cancer pathogenesis.
Main Methods:
- Combined bisulfite restriction analysis (COBRA) and pyrosequencing to assess miRNA promoter methylation.
- RT-qPCR to determine gene expression levels.
- Correlation analysis of miRNA methylation with clinicopathologic factors in 252 gynecological specimens.
Main Results:
- Thirteen miRNA loci targeting SOX4 3'-UTR were identified in silico.
- Increased methylation of miR-203, miR-219-2, miR-596, and miR-618 was observed in endometrial cancer cells.
- miR-203 mimic transfection reduced SOX4 expression; miR-203 hypermethylation occurred in 52% of endometrioid endometrial carcinomas and correlated with microsatellite instability and MLH1 methylation.
Conclusions:
- miR-203 hypermethylation is a frequent event in endometrial carcinomas.
- miR-203 methylation is strongly associated with microsatellite instability and MLH1 methylation status.
- miR-203 methylation may serve as a potential biomarker for endometrioid and clear cell endometrial cancer subtypes.
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