Transcriptional regulation of thymine DNA glycosylase (TDG) by the tumor suppressor protein p53

Costa, Nathalia Meireles Da; Hautefeuille, A.; Cros, Marie-Pierre; Melendez, Matias Eliseo; Waters, T.P.; Swann, Peter F.; Hainaut, Pierre; Pinto, Luís Felipe Ribeiro

doi:10.4161/cc.22843

Cited by 22 publications

(17 citation statements)

References 65 publications

(80 reference statements)

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“…Moreover, p53 transcriptionally regulates TDG expression by binding to the TDG promoter and regulating TDG nuclear translocation. These findings certainly support the hypothesis that TDG is a candidate for inclusion in the family of tumor suppressors [60].…”

Section: Tdg In Development and Cancersupporting

confidence: 77%

Multifaceted roles for thymine DNA glycosylase in embryonic development and human carcinogenesis

Xu¹,

Watt²,

Liu³

2016

ABBS

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Section: Tdg In Development and Cancersupporting

confidence: 77%

Multifaceted roles for thymine DNA glycosylase in embryonic development and human carcinogenesis

Xu¹,

Watt²,

Liu³

2016

ABBS

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“…The direct interactions between miR-29b and TET1, TDG and DNMT3A were confirmed by luciferase assays and western blot analysis (16). Although there are numerous pathways that regulate the levels of TET1 (13,20), TDG (21) and DNMT3A (22) in breast cancer, significant inverse correlations were identified between the expression levels of miR-29b and DNMT3A in ER-positive patients. The overexpression of DNMT3A correlates with a poor prognosis in numerous cancers, including breast cancer (10,23).…”

Section: Discussionmentioning

confidence: 84%

miR-29b is an indicator of prognosis in breast cancer patients

Shinden

Iguchi

Akiyoshi

et al. 2015

Molecular and Clinical Oncology

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Abstract. MicroRNA-29b (miR-29b) targets numerous important genes that mediate carcinogenesis and tumor development in breast cancer in vitro and in vivo. The aim of the present study was to determine the clinical significance of miR-29b expression in primary breast cancer patients. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) of miR-29b and certain target genes of miR-29b, such as DNA methyltransferase 3A (DNMT3A), ten-eleven translocation 1 (TET1) and thymine DNA glycosylase (TDG), was performed in 94 primary breast cancer samples. Low expression of miR-29b in primary tumors was significantly associated with poorer disease-free survival (DFS) (P=0.0075) and overall survival (OS) (p=0.0012). Multivariate analysis indicated that miR-29b expression was an independent prognostic factor for OS [relative risk=15.6 (2.33-348), P=0.0026]. In addition, a significant inverse correlation was identified between the expression levels of DNMT3A and miR-29b in estrogen receptor-positive breast cancer patients (P=0.027). To the best of our knowledge, this is the first study to investigate the clinicopathological significance of miR-29b in breast cancer cases and miR-29b is shown to act as a tumor suppressive microRNA in breast cancer and as a potential marker for recurrence and metastasis in breast cancer patients. IntroductionBreast cancer is a leading cause of cancer-related mortality among women in industrialized countries. Despite advances in the technologies used for its diagnosis and treatment, recurrence and metastasis of breast cancer remain serious clinical issues. Therefore, there is an urgent need to identify biomarkers or techniques to be used for the early detection of carcinogenesis or recurrence following curative surgery using minimally invasive tests.MicroRNAs (miRs) are small non-coding RNAs consisting of 20-22 nucleotides. Changes in the levels of miRs are involved in the initiation and progression of human cancers due to the altered translation of various target genes (1). The recent increase in miR interest is attributed to the breakthrough discovery of their role in numerous pathological processes, including malignant transformation (2). In fact, miRs have been reported as potential biomarkers of various malignancies (3,4).MicroRNA-29b (miR-29b) regulates a number of important genes that mediate carcinogenesis and tumor development in breast cancer (5-8). For example, miR-29b targets a network of pro-metastatic regulators involved in angiogenesis, collagen remodeling and proteolysis, thereby inhibiting metastasis (5). Furthermore, miR-29b directly targets DNA methyltransferase 3A (DNMT3A), DNMT3B, ten-eleven translocation 1 (TET1) and thymine DNA glycosylase (TDG), all of which play crucial roles in the progression and metastasis of various cancers by altering the DNA methylation status (9-16). Although almost all the studies investigating the numerous important roles of miR-29b in breast cancer have been experimental studies conducted in vitro and in vivo (5)(6)(7)(8)16), the c...

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“…Because TDG is required for DNA repair and demethylation, it may play a role in tumor prevention, a role supported by a report that TDG acts as a coactivator of p53 (22,23), which binds the TDG promoter and regulates TDG transcription (24). In the human genome, the TDG gene is located on chromosome 12q24.1.…”

Section: Colorectal Cancer (Crc)mentioning

confidence: 97%

Thymine DNA Glycosylase Is a Positive Regulator of Wnt Signaling in Colorectal Cancer

Shi

et al. 2014

Journal of Biological Chemistry

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Transcriptional regulation of thymine DNA glycosylase (TDG) by the tumor suppressor protein p53

Abstract: (2012) Transcriptional regulation of thymine DNA glycosylase (TDG) by the tumor suppressor protein p53, Cell Cycle, 11:24,[4570][4571][4572][4573][4574][4575][4576][4577][4578]

Cited by 22 publications

References 65 publications

Multifaceted roles for thymine DNA glycosylase in embryonic development and human carcinogenesis

Multifaceted roles for thymine DNA glycosylase in embryonic development and human carcinogenesis

miR-29b is an indicator of prognosis in breast cancer patients

Thymine DNA Glycosylase Is a Positive Regulator of Wnt Signaling in Colorectal Cancer

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