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Association of TET1 expression with colorectal cancer progression
Yiping Tian1,2,3, Feixia Pan4, Xiaohui Sun4
1a Department of Pathology , Zhejiang University School of Medicine , Hangzhou , China.
Objective:
The ten-eleven translocation (TET) proteins, as methylcytosine dioxygenases, catalyze 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC). The altered expression of TET1 disrupts the balance between DNA methylation and demethylation. This alteration has been reported to be associated with carcinogenesis in various malignancies. The aim of the present study was to investigate changes in expression and the role of TET1 in colorectal cancer (CRC).
Material And Methods:
A total of 109 CRC patients who underwent radical surgical colon resection were enrolled. The QuantiGene Plex Assay was used to detect the expression of TET1 in CRC tissues and matching adjacent normal tissues. We analyzed the associations between TET1 expression levels and various clinicopathologic features of CRC. TET1 overexpression and depletion cells were constructed to investigate its biological role in CRC.
Results:
Compared to normal tissues, the expression level of TET1 in CRC was significantly lower. The ratio of TET1 in CRC tissues to that in adjacent normal tissues (C/N-TET1) was an independent overall survival predictive factor. Moreover, in vitro studies showed that TET1 could inhibit cell growth and promote cell metastasis and invasion.
Conclusions:
These findings indicated that TET1 played a multifaceted role in the pathogenesis of CRC, and thereby resulting in multiple effects on tumor progression.
Insights
Ten-eleven translocation 1 (TET1) expression is reduced in colorectal cancer (CRC), impacting DNA methylation. Lower TET1 levels predict poor survival and influence tumor progression, highlighting its complex role in CRC pathogenesis.
Area of Science:
- Molecular biology
- Genetics
- Cancer research
Background:
- Ten-eleven translocation (TET) proteins are methylcytosine dioxygenases involved in DNA demethylation.
- Altered TET1 expression is linked to various cancers, disrupting DNA methylation balance.
- Investigating TET1's role in colorectal cancer (CRC) is crucial for understanding tumorigenesis.
Purpose of the Study:
- To examine TET1 expression changes in colorectal cancer (CRC) tissues.
- To determine the association between TET1 expression and CRC clinicopathologic features.
- To elucidate the biological role of TET1 in CRC progression.
Main Methods:
- QuantiGene Plex Assay used to measure TET1 expression in 109 CRC patients' tissues and adjacent normal tissues.
- Analysis of correlations between TET1 levels and clinicopathologic characteristics.
- In vitro studies involving TET1 overexpression and depletion cell models.
Main Results:
- TET1 expression was significantly lower in CRC tissues compared to normal tissues.
- The TET1 ratio in tumor vs. normal tissue (C/N-TET1) independently predicted overall survival.
- In vitro, TET1 inhibited cell growth but promoted metastasis and invasion.
Conclusions:
- TET1 plays a complex, multifaceted role in colorectal cancer (CRC) pathogenesis.
- Altered TET1 expression influences multiple aspects of tumor progression in CRC.
- TET1's dual role in inhibiting growth and promoting metastasis warrants further investigation in CRC.
