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Updated: Nov 3, 2025
Continuous Fluorescence-Based Endonuclease-Coupled DNA Methylation Assay to Screen for DNA Methyltransferase Inhibitors
Published on: August 5, 2022
TSHZ3 functions as a tumor suppressor by DNA methylation in colorectal cancer
Youxin Zhou1, Sentai Wang1, Xuequn Yin2
1Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China.
Objective:
Teashirt zinc finger homeobox 3 (TSHZ3) is currently reported to be aberrantly expressed in several tumors, but the detailed functions and epigenetic mechanisms of TSHZ3 in colorectal cancer (CRC) remain unclear.
Materials And Methods:
In this study, the TSHZ3 expression in 118 CRC and normal adjacent tissues (NATs) was evaluated, and the methylation status of the TSZH3 promoter region in CRC tissues and cell lines was also analyzed.
Results:
The results of PCR analysis showed that TSHZ3 was significantly down-regulated in CRC tissues, and patients with low TSHZ3 levels had a poorer 5-year overall survival (OS) rate. Analyzing the promoter sequence (-1000∼0) by MethPrimer, TSHZ3 promoter was found to harbor abundant of CpG islands. The methylation specific PCR (MSP) analysis presented a relatively hypermethylated status of THSZ3 promoter in CRC samples. The data of MSP and bisulfite sequencing PCR (BSP) also confirmed that CpG sites of TSHZ3 promoter were methylated in CRC cells, and the DNA methyltransferase (DNMT) inhibitor 5-aza-2'-deoxycytidine (5-Aza) could effectively restored the TSHZ3 expression in vitro. Functionally, the proliferation, apoptosis and metastasis of CRC cells were regulated by TSZH3 over-expression, and the suppressing effects of TSHZ3 in CRC were also confirmed in a xenograft mouse model.
Conlusions:
Our results indicated that promoter methylation was one of the mechanisms contributing to the down-regulation of TSHZ3 in CRC, and TSZH3 might served as a potential tumor suppressor gene in the development and progression of CRC.
Insights
TSHZ3 is downregulated in colorectal cancer (CRC) due to promoter methylation. Restoring TSHZ3 expression suppressed CRC cell proliferation and metastasis, indicating its role as a tumor suppressor.
Area of Science:
- Oncology
- Molecular Biology
- Epigenetics
Background:
- Teashirt zinc finger homeobox 3 (TSHZ3) expression is altered in various tumors.
- The specific functions and epigenetic regulation of TSHZ3 in colorectal cancer (CRC) are not well understood.
Purpose of the Study:
- To investigate the expression levels and epigenetic mechanisms of TSHZ3 in colorectal cancer.
- To determine the functional role of TSHZ3 in CRC development and progression.
Main Methods:
- TSHZ3 expression and promoter methylation were analyzed in 118 CRC and normal adjacent tissues (NATs) and CRC cell lines.
- Methylation-specific PCR (MSP), bisulfite sequencing PCR (BSP), and xenograft mouse models were employed.
- The effect of DNA methyltransferase (DNMT) inhibitor 5-aza-2'-deoxycytidine (5-Aza) on TSHZ3 expression was assessed.
Main Results:
- TSHZ3 was significantly downregulated in CRC tissues, correlating with poorer 5-year overall survival (OS).
- TSHZ3 promoter exhibited hypermethylation in CRC samples and cell lines.
- TSHZ3 overexpression suppressed CRC cell proliferation, apoptosis, and metastasis in vitro and in vivo.
Conclusions:
- Promoter methylation is a key mechanism for TSHZ3 downregulation in CRC.
- TSHZ3 functions as a tumor suppressor gene in colorectal cancer development and progression.
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