Yiping Tian1,2,3, Feixia Pan4, Xiaohui Sun4, Meifu Gan5, Aifen Lin6, Dandan Zhang1,2, Yimin Zhu3, Maode Lai1,2. 1. a Department of Pathology , Zhejiang University School of Medicine , Hangzhou , China. 2. b Key Laboratory of Disease Proteomics of Zhejiang Province , Hangzhou , China. 3. c Pathology Department , Zhejiang Cancer Hospital , Hangzhou , China. 4. d Department of Epidemiology and Biostatistics , Zhejiang University School of Public Health , Hangzhou , China. 5. e Department of Pathology , Taizhou Hospital , Linhai , China. 6. f Medical Research Center, Taizhou Hospital of Zhejiang Province, Wenzhou Medical University , Linhai , China.
Abstract
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.
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.