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      C-terminal binding protein-2 is a prognostic marker for lung adenocarcinomas

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          Abstract

          C-terminal binding protein-2 (CtBP2) a transcriptional corepressor, has been reported to involve in tumorigenesis and progression and predict a poor prognosis in several human cancers. However, few studies on CtBP2 in lung cancer tissues have been performed. In the present study, we first explored the CtBP2 gene expression profile from the the cancer genome atlas (TCGA) datasets, then western blot analysis and immunohistochemistry were performed to investigate and verified whether lung adenocarcinoma (LUAD) tissues exhibit deregulated CtBP2 expression. We evaluated the correlations between CtBP2 expression and the clinicopathological characteristics, and Kaplan–Meier survival analyses were performed to estimate the effect of CtBP2 expression on prognosis of LUAD patients. The results revealed that CtBP2 expression was significantly upregulated in LUAD tissues compared with normal lung tissues. Furthermore, increasing CtBP2 expression in LUAD was significantly associated with tumor differentiation ( P = .028), tumor node metastasis (TNM) stage ( P = .042). CtBP2 expression was significantly correlated with LUAD patients’ survival ( P = .028). In conclusion, the present study revealed that CtBP2 protein is a novel prognostic marker for LUAD. A further large-scale study is needed to confirm the present results.

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          Most cited references23

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          CtBP, an unconventional transcriptional corepressor in development and oncogenesis.

          CtBP family proteins are conserved among vertebrates and invertebrates and function as transcriptional corepressors. They repress transcription in a histone deacetylase-dependent or -independent manner. CtBPs play important roles during development and oncogenesis. In this review, their unusual properties, the mechanisms of transcriptional repression, regulation, and their biological functions are discussed.
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            Transcriptional regulation by C-terminal binding proteins.

            C-terminal binding protein family members function predominantly as transcriptional corepressors in association with sequence specific DNA-binding transcriptional repressors. The vertebrates have two CtBP genes while the invertebrates contain a single gene. Genetic studies indicate that the CtBP genes play pivotal roles in animal development. The vertebrate C-terminal binding proteins (CtBP1 and CtBP2) are highly related and are functionally redundant for certain developmental processes and non-redundant for others. The animal C-terminal binding proteins exhibit structural and functional similarity to d-isomer-specific 2-hydroxy acid dehydrogenases (D2-HDH). They function as dimers, recruiting transcriptional regulators through two protein-binding interfaces in each monomer. The corepressor complex of CtBP1 contains enzymatic constituents that mediate coordinated histone modification by deacetylation and methylation of histone H3-Lysine 9 and demethylation of histone H3-Lysine 4. CtBP also recruits the small ubiquitin-related modifier (SUMO) conjugating E2 enzyme UBC9 and a SUMO E3 ligase (HPC2), suggesting that CtBP-mediated transcriptional regulation may also involve SUMOylation of transcription factors. In addition to gene-specific transcriptional repression, CtBP1 appears to antagonize the activity of the global transcriptional coactivators, p300/CBP. Genetic evidence also suggests that the fly CtBP (dCtBP) and the vertebrate CtBP2 might activate transcription in a context-dependent manner. The transcriptional regulatory activity of CtBP is modulated by the nuclear NADH/NAD+ ratio and hence appears to be influenced by the metabolic status of the cell. The nuclear dinucleotide ratio may differentially influence the repression activities of factors that recruit CtBP through PLDLS-like motifs and those through non-PLDLS-motifs.
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              Genome-wide profiles of CtBP link metabolism with genome stability and epithelial reprogramming in breast cancer

              The C-terminal binding protein (CtBP) is a NADH-dependent transcriptional repressor that links carbohydrate metabolism to epigenetic regulation by recruiting diverse histone modifying complexes to chromatin. Here, global profiling of CtBP in breast cancer cells reveals that it drives epithelial to mesenchymal transition, stem cell pathways, and genome instability. CtBP expression induces mesenchymal and stem cell-like features while CtBP depletion or caloric restriction reverses gene repression and increases DNA repair. Multiple members of the CtBP-targeted gene network are selectively down-regulated in aggressive breast cancer subtypes. Differential expression of CtBP-targeted genes predicts poor clinical outcome in breast cancer patients, and elevated levels of CtBP in patient tumors predict shorter median survival. Finally, both CtBP promoter targeting and gene repression can be reversed by small molecule inhibition. These findings define broad roles for CtBP in breast cancer biology and suggest novel chromatin-based strategies for pharmacologic and metabolic intervention in cancer.
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                Author and article information

                Journal
                Medicine (Baltimore)
                Medicine (Baltimore)
                MEDI
                Medicine
                Wolters Kluwer Health
                0025-7974
                1536-5964
                31 July 2020
                31 July 2020
                : 99
                : 31
                : e20076
                Affiliations
                [a ]Department of Thoracic Surgery, Hubei Cancer Hospital
                [b ]Department of Tongji Hospital of Thoracic Surgery, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei, China.
                Author notes
                []Correspondence: Baoguo Yan, Department of Thoracic Surgery, Hubei Cancer Hospital, 116 Zhudao Spring South Road, Hongshan District, Wuhan, Hubei, China (e-mail: 492732499@ 123456qq.com ).
                Article
                MD-D-19-01779 20076
                10.1097/MD.0000000000020076
                7402787
                32756072
                098c1c9f-203a-44e6-9dd2-9e16cda90557
                Copyright © 2020 the Author(s). Published by Wolters Kluwer Health, Inc.

                This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial License 4.0 (CCBY-NC), where it is permissible to download, share, remix, transform, and buildup the work provided it is properly cited. The work cannot be used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc/4.0

                History
                : 23 March 2019
                : 31 March 2020
                : 1 April 2020
                Categories
                5700
                Research Article
                Observational Study
                Custom metadata
                TRUE

                c-terminal binding protein-2,lung adenocarcinoma,lung cancer,tumor marker

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