Potential of 5-hmC and TET Expression as Cancer Biomarkers
The role of epigenetics in cancer and developmental biology has become the focus of extensive research. 5-hydoxymethylcytosine (5-hmC) is an epigenetic modification that arises from the oxidation of 5-methylcytosine (5-mC) by the epigenetic regulatory proteins belonging to the TET (ten-eleven translocation) family of α-ketoglutarate-dependent deoxygenases. The TET enzymes are responsible for much of the plasticity of cytosine specific modifications. TETs catalyze the progressive oxidation of 5-mC through 5-carboxylcytosine (5-caC), which eventually leads to decarboxylation. TET2 is a known tumor suppressor and is frequently inhibited in cancer cells by two methods: loss of function mutagenesis and competitive inhibition by a 2-hydroxyglutarate.
In addition to these inhibitory mechanisms Yang et al. showed that mRNA levels for TET family members were reduced in cancer cells, indicating there was also inhibition of gene expression at the transcriptional level. Directly correlated to the inhibition of TET, it was found that there was a marked reduction in 5-hmC in cancer tissues relative to surrounding normal tissues.
This result was confirmed in liver, lung and pancreatic cancers, and is in agreement with a previous finding that showed decreased levels of 5-hmC in breast, colon, and prostate cancer. These results indicate the importance of 5-hmC/TET in gene regulation and the potential value of 5-hmC as a biomarker for cancer.
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Yang, H., Y. Liu, F. Bai, J-Y Zang, S-H Ma, J. Liu, Z-D Xu, H-G Xu, Z-Q Ling, D. Ye, K-L Guan, and Y. Xiong.