Journal
SURGICAL ONCOLOGY-OXFORD
Volume 27, Issue 1, Pages 76-81Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.suronc.2017.12.004
Keywords
Colorectal cancer; microRNA; Epigenetics; miR-21; TET1
Funding
- Taiwan's Ministry of Science and Technology [MOST103-2320-B-038-052, MOST104-2320-B-038-005, MOST105-2320-B-038-002]
- Taipei Medical University [TMU103-AE2-I04-4, TMU104-AE2-I02-4, TMU105-AE2-I03-4, TMU106-F-005]
- Comprehensive Cancer Center of Taipei Medical University - Health and Welfare Surcharge of Tobacco Products [MOHW106-TDU-B212-144001]
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DNA 5-methylcytosine (5-mC) methylation, a key epigenetic mark, is critical for biological and pathological processes. Aberrant DNA methylation occurs in all tumor types and correlates with tumor suppressor gene silencing. DNA methylation is thought to be very stable, and active DNA demethylation remains a long-standing enigma. Recently, the ten-eleven translocation (TET) family of oxygenases are found to oxidize 5-mC to 5-hydroxymethylcytosine (5-hmC), which is prerequisite for active DNA demethylation. Both TET1 expression and global 5-hmC content are significantly reduced in colorectal cancer (CRC), the top leading cause of cancer-related death in the world. However, the involving molecular mechanisms are still unclear. The oncogenic microRNA (miRNA) miR-21-5p has recently identified as a diagnostic and prognostic biomarker in CRC. In this study, TET1 was predicted as a novel target of miR-21-5p by using a web-based predictive software starBase v2.0. We found that the 3'-UTR region of TET1 gene contains a miR-21-5p-binding site. Examination of tumor tissues from CRC patients found that loss of TET1 was associated with the progression of CRC to advance stages. In addition, negative correlation of miR-21-5p and TET1 expression was also observed. Transfection of the synthetic miR-21-5p mimic or inhibitor into the colorectal cancer cells could inhibit or increase the TET1-30-UTR luciferase activity, respectively. Our results demonstrate that TET1 is a potential target of miR-21-5p in CRC. (C) 2018 Elsevier Ltd. All rights reserved.
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