Multiple Functions of Ten-eleven Translocation 1 during Tumorigenesis

Objective： Aberrant expression of ten-eleven translocation 1 （TET1） plays a critical role in tumor development and progression. We systematically summarized the latest research progress on the role and mechanisms of TET1 in cancer biology. Data Sources： Relevant articles published in English from 1980 to April 2016 were selected from the PubMed database. Tile terms ＂＇ten-eleven translocation 1,＂ ＂＇SmC,＂ ＇5hmC,＂ ＇microRNA,＇＂ ＂hypoxia,＂ and ＂＇embryonic stem cell＇＂ were used tbr the search. Study Selection： Articles focusing on the role and mechanism ofTETI in tumor were reviewed, including clinical and basic research articles. Results： TET proteins, the key enzymes converting 5-methylcytosine to 5-hydroxymethylcytosine, play vital roles in DNA demethylation regulation. Recent studies have shown that loss of TETI is associated with tumorigenesis and can be used as a potential biomarker for cancer therapy, which indicates that TETI serves as tumor suppressor gene. Moreover, besides its dioxygenase activity, TET1 could induce epithelial-mesenchymal transition and act as a coactivator to regulate gene transcription, such as developmental regulator in embryonic stem cells （ESCs） and hypoxia-responsive gene in cancer. The regulation of TETl is also correlated with microRNA in a posttranscriptional modification process. Hence, it is complex but critical to coaprehend the mechanisms of TETI in the biology of ESCs and cancer. Conclusions： TET I not only serves as a demethylation enzyme but also plays multiple roles during tumorigenesis and progression. More studies should be carried out to elucidate the exact mechanisms of TETI and its associations with cancer betbre considering it as a therapeutic tool.

RegIV expression showing specificity to gastrointestinal tract and its potential role in diagnosing digestive tract neuroendocrine tumor

Regenerating gene IV （RegIV）, a member of the regenerating gene family discovered in 2001, has been found to be involved in malignancy in several different organs including the stomach, colorectum, pancreas and prostate, but the overall expression profile of RegIV has not been reported. To learn more about RegIV, we evaluated its distribution by immunohistochemistry （IHC） in a total of 360 samples including 24 types of normal tissue, 40 benign and malignant lesions, and 18 neuroendocrine tumors. We found that in normal tissues, in addition to its relative specificity for the gastrointestinal tract, RegIV was detected in the adrenal gland and mammary gland. Among all the malignancies of various histological types under evaluation, RegIV was found mostly in adenocarcinomas. Studies on additional sets of colorectal tumor samples showed that RegIV expression was predominant in colorectal adenoma （87.5%） and peritumoral tissue （100%） but not in cancer tissue （30.8%）. Among neuroendocrine tumors, ReglV had a relatively restricted expression to those of digestive system.

Global changes of 5-hydroxymethylcytosine and 5-methylcytosine from normal to tumor tissues are associated with carcinogenesis and prognosis in colorectal cancer

Aberrant DNA methylation has raised widespread attention in tumorigenesis. In this study, we aimed to investigate the changes of global DNA methylation and hydroxymethylation from normal to tumor tissues in colorectal cancer(CRC) and their association with the prognosis. The levels of genomic 5-hydroxymethylcytosine(5hmC) and 5-methylcytosine(5mC) in cancerous tissues were significantly lower than those in corresponding adjacent normal tissues. The genomic levels of 5mC were significantly positively correlated with 5hmC in normal and cancerous tissues(all P<0.05). The ratio of 5mC in cancerous tissues to matched normal tissues(C/N-5mC) was also significantly positively correlated with the ratio of 5hmC in cancerous tissues to matched normal tissues(C/N-5hmC)(P=0.01). The 5mC levels and C/N-5mC ratios decreased with age(all P<0.05). Higher 5mC and 5hmC levels were found in rectal than in colon tissues(all P<0.05). High levels of 5mC in cancerous tissues and high C/N-5hmC ratios were each associated with lymph node metastasis(all P<0.05). Survival analysis indicated that the C/N-5mC ratio(P=0.04) is an independent protective factor for overall survival. The data showed that patients with a combination of high C/N-5hmC and low C/N-5mC ratios tended to have a worse prognosis(P<0.01). Our findings showed that the C/N-5mC ratio may be an independent prognostic factor for CRC outcome. Patients with both a high C/N-5hmC ratio and a low C/N-5mC ratio exhibited the worst survival, suggesting that 5mC and 5hmC can be used as critical markers in tumorigenesis and prognosis estimation.