Purpose: Lung adenocarcinoma (LUAD) is one of the most common cancers worldwide. The THanatos-Associated Proteins (THAP) family plays an essential role in multiple cancers. However, the role of THAP7 in cancers has remained elusive.
Methods: THAP7 expression status in LUAD tissues was analysed by using the Oncomine database and qRT-PCR, and its expression level in LUAD cell lines was detected by qRT-PCR and Western blotting. The role of THAP7 in LUAD cells was determined by proliferation, colony formation, and cell cycle analyses. In vivo role of THAP7 was studied on xenograft models. Luciferase reporter assays and chromatin immunoprecipitation (ChIP) were used to determine the activity and acetylation of the p21 promoter.
Results: THAP7 expression was increased in LUAD tissues and cell lines. Moreover, the high expression of THAP7 was correlated with poor prognosis. The overexpression of THAP7 accelerated the G1/S phase transition and promoted tumour growth both in vitro and in vivo. A mechanistic study revealed that THAP7 reduced the acetylation of histone H3 on the p21 promoter to suppress p21 transcription.
Conclusion: For the first time, we demonstrated the function of THAP7 in LUAD, and our findings suggested that THAP7 may be a potential molecular therapy target in LUAD.
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http://dx.doi.org/10.2147/OTT.S208908 | DOI Listing |
Zhongguo Fei Ai Za Zhi
January 2024
Health Company of PLA 68303 Troops, Baiyin 730900, China.
Background: Lung cancer is a major threat to human health. The molecular mechanisms related to the occurrence and development of lung cancer are complex and poorly known. Exploring molecular markers related to the development of lung cancer is helpful to improve the effect of early diagnosis and treatment.
View Article and Find Full Text PDFOnco Targets Ther
July 2019
Department of Thoracic Oncology, The Cancer Center of the Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong 519000, People's Republic of China.
Purpose: Lung adenocarcinoma (LUAD) is one of the most common cancers worldwide. The THanatos-Associated Proteins (THAP) family plays an essential role in multiple cancers. However, the role of THAP7 in cancers has remained elusive.
View Article and Find Full Text PDFJ Cell Biochem
September 2007
Department of Cell Biology and Cancer Center, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA.
HiNF-P is a recently identified histone H4 subtype specific transcriptional regulator that associates with the conserved cell cycle control element in the proximal promoter regions of histone H4 genes. HiNF-P interacts with the global histone gene regulator and direct cyclin E/CDK2 substrate p220(NPAT) to potently upregulate histone H4 gene transcription at the G1/S phase transition in response to cyclin E/CDK2 signaling. To gain insight into the function of HiNF-P in a broader cellular context, we performed a yeast two-hybrid screen to identify its novel interacting proteins.
View Article and Find Full Text PDFMol Endocrinol
February 2006
Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, USA.
The posttranslational modifications of histones on chromatin or a lack thereof is critical in transcriptional regulation. Emerging studies indicate a role for histone-binding proteins in transcriptional activation and repression. We have previously identified template-activating factor-Ibeta (TAF-Ibeta, also called PHAPII, SET, and I(2)(pp2A)) as a component of a cellular complex called inhibitor of acetyltransferases (INHAT) that masks histone acetylation in vitro and blocks histone acetyltransferase (HAT)-dependent transcription in living cells.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
May 2005
Laboratoire de Biologie Vasculaire, Equipe Labellisée La Ligue 2003, Institut de Pharmacologie et de Biologie Structurale, Centre National de la Recherche Scientifique Unité Mixte de Recherche 5089, 205 Route de Narbonne, 31077 Toulouse, France.
We have recently described an evolutionarily conserved protein motif, designated the THAP domain, which defines a previously uncharacterized family of cellular factors (THAP proteins). The THAP domain exhibits similarities to the site-specific DNA-binding domain of Drosophila P element transposase, including a putative metal-coordinating C2CH signature (CX(2-4)CX(35-53)CX(2)H). In this article, we report a comprehensive list of approximately 100 distinct THAP proteins in model animal organisms, including human nuclear proapoptotic factors THAP1 and DAP4/THAP0, transcriptional repressor THAP7, zebrafish orthologue of cell cycle regulator E2F6, and Caenorhabditis elegans chromatin-associated protein HIM-17 and cell-cycle regulators LIN-36 and LIN-15B.
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