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Tytuł:
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The oncogenic role of TFAP2A in bladder urothelial carcinoma via a novel long noncoding RNA TPRG1-AS1/DNMT3A/CRTAC1 axis.
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Autorzy:
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He J; Department of Surgical Oncology and Breast Surgery, The First Hospital of China Medical University, Shenyang 110001, Liaoning, PR China.
Dong C; Department of Urology, The First Hospital of China Medical University, Shenyang 110001, Liaoning, PR China; Institute of Urology, China Medical University, Shenyang 110001, Liaoning, PR China.
Zhang H; Department of Urology, The First Hospital of China Medical University, Shenyang 110001, Liaoning, PR China; Institute of Urology, China Medical University, Shenyang 110001, Liaoning, PR China.
Jiang Y; Department of Urology, The First Hospital of China Medical University, Shenyang 110001, Liaoning, PR China; Institute of Urology, China Medical University, Shenyang 110001, Liaoning, PR China.
Liu T; Department of Urology, The First Hospital of China Medical University, Shenyang 110001, Liaoning, PR China; Institute of Urology, China Medical University, Shenyang 110001, Liaoning, PR China.
Man X; Department of Urology, The First Hospital of China Medical University, Shenyang 110001, Liaoning, PR China; Institute of Urology, China Medical University, Shenyang 110001, Liaoning, PR China. Electronic address: .
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Źródło:
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Cellular signalling [Cell Signal] 2023 Feb; Vol. 102, pp. 110527. Date of Electronic Publication: 2022 Nov 21.
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Typ publikacji:
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Journal Article; Research Support, Non-U.S. Gov't
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Język:
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English
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Imprint Name(s):
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Publication: Oxford : Elsevier Science Ltd
Original Publication: Oxford ; New York : Pergamon Press, 1988-
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MeSH Terms:
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Carcinoma, Transitional Cell*
MicroRNAs*/metabolism
RNA, Long Noncoding*/genetics
RNA, Long Noncoding*/metabolism
Transcription Factor AP-2*/genetics
Transcription Factor AP-2*/metabolism
Urinary Bladder Neoplasms*/genetics
Urinary Bladder Neoplasms*/pathology
Humans ; Adenosine Triphosphate ; Calcium-Binding Proteins/metabolism ; Cell Line, Tumor ; Cell Proliferation/genetics ; Gene Expression Regulation, Neoplastic ; Glucose ; Lactates ; Urinary Bladder/metabolism
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Contributed Indexing:
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Keywords: Bladder urothelial carcinoma; CRTAC1; DNMT3A; Long noncoding RNA TPRG1-AS1; TFAP2A
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Substance Nomenclature:
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8L70Q75FXE (Adenosine Triphosphate)
0 (Calcium-Binding Proteins)
0 (CRTAC1 protein, human)
IY9XDZ35W2 (Glucose)
0 (Lactates)
0 (MicroRNAs)
0 (RNA, Long Noncoding)
0 (TFAP2A protein, human)
0 (Transcription Factor AP-2)
0 (DNMT3A protein, human)
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Entry Date(s):
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Date Created: 20221121 Date Completed: 20230105 Latest Revision: 20230318
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Update Code:
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20240104
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DOI:
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10.1016/j.cellsig.2022.110527
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PMID:
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36410635
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Background: Overexpression of TFAP2A has been linked to increased lymph node metastasis in basal-squamous bladder cancer. However, its downstream targets in bladder urothelial carcinoma (BLCA), the most malignant cancer of the urinary tract, remain unclear. In the current study, we aim to explore the function and mechanism of TFAP2A in BLCA.
Methods: TFAP2A expression and the prognostic significance in BLCA was analyzed using TCGA and GTEX projects. TFAP2A was knocked-down in BLCA cells to study its impact on glucose uptake, lactate and ATP production, expression of HK2, and the number of vascular meshes formed by HUVEC. The target long noncoding RNAs (lncRNAs) of TFAP2A were predicted by bioinformatics tools, followed by ChIP-qPCR and luciferase assays. The downstream targets of TPRG1-AS1 were analyzed by microarray analysis. Rescue experiments were conducted for validation.
Results: TFAP2A upregulation in BLCA predicted dismal survival of patients. Loss of TFAP2A inhibited glycolysis (as evidenced by reduced glucose uptake, lactate, ATP production, and the expression of HK2) and angiogenesis (decreased number of vascular meshes formed by HUVEC). TFAP2A promoted the transcription of TPRG1-AS1. TPRG1-AS1 reversed the inhibitory effect of TFAP2A knockdown on glycolysis and angiogenesis in BLCA cells. TPRG1-AS1 inhibited the transcription of CRTAC1 by recruiting a DNA methyltransferase to the promoter of CRTAC1 and increasing the DNA methylation of its promoter. CRTAC1 inhibited glycolysis and angiogenesis in BLCA cells. TFAP2A silencing curbed tumor growth in vivo via the TPRG1-AS1/CRTAC1 axis.
Conclusion: TFAP2A reduces CRTAC1 expression by promoting TPRG1-AS1 transcription, thereby expediting BLCA glycolysis and angiogenesis.
Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to report.
(Copyright © 2022 Elsevier Inc. All rights reserved.)
