Involvement of GTA protein NC2β in Neuroblastoma pathogenesis suggests that it physiologically participates in the regulation of cell proliferation

Pietro, Cinzia Di; Ragusa, Marco; Barbagallo, Davide; Duro, Laura R.; Guglielmino, Maria Rosa; Majorana, Alessandra; Giunta, Veronica; Rapisarda, A.; Tricarichi, Elisa; Miceli, Marco; Angelica, Rosario; Grillo, Agata; Banelli, Barbara; Defferari, I; Forte, Stefano; Laganà, Alessandro; Bosco, Camillo; Giugno, Rosalba; Pulvirenti, Alfredo; Ferro, Alfredo; Grzeschik, K.-H.; Cataldo, Andrea Di; Tonini, Gian Paolo; Romani, Massimo; Purrello, Michele

doi:10.1186/1476-4598-7-52

Cited by 5 publications

(3 citation statements)

References 46 publications

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“…Overexpression of DGUOK has been associated with worse prognosis in lung cancer, and its depletion suppressed lung adenocarcinoma growth, CSC self-renewal and metastasis ( 31 ). GTF2B has been identified as a prognostic marker for colorectal cancer and neuroblastoma, while GTF2H1 is a p62 subunit of complex transcription factor IIH (TFIIH) that regulates nucleotide excision repair and transcription ( 32 , 33 ). Certain polymorphisms/haplotypes of GTF2H1 have been associated with increased susceptibility to lung cancer ( 34 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of DNA repair gene signature and potential molecular subtypes in hepatocellular carcinoma

Bai¹,

He²,

Ma³

et al. 2023

Front. Oncol.

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DNA repair is a critical factor in tumor progression as it impacts tumor mutational burden, genome stability, PD-L1 expression, immunotherapy response, and tumor-infiltrating lymphocytes (TILs). In this study, we present a prognostic model for hepatocellular carcinoma (HCC) that utilizes genes related to the DNA damage response (DDR). Patients were stratified based on their risk score, and groups with lower risk scores demonstrated better survival rates compared to those with higher risk scores. The prognostic model’s accuracy in predicting 1-, 3-, and 5-year survival rates for HCC patients was analyzed using receiver operator curve analysis (ROC). Results showed good accuracy in predicting survival rates. Additionally, we evaluated the prognostic model’s potential as an independent factor for HCC prognosis, along with tumor stage. Furthermore, nomogram was employed to determine the overall survival year of patients with HCC based on this independent factor. Gene set enrichment analysis (GSEA) revealed that in the high-risk group, apoptosis, cell cycle, MAPK, mTOR, and WNT cascades were highly enriched. We used training and validation datasets to identify potential molecular subtypes of HCC based on the expression of DDR genes. The two subtypes differed in terms of checkpoint receptors for immunity and immune cell filtration capacity.Collectively, our study identified potential biomarkers of HCC prognosis, providing novel insights into the molecular mechanisms underlying HCC.

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Section: Discussionmentioning

confidence: 99%

Identification of DNA repair gene signature and potential molecular subtypes in hepatocellular carcinoma

Bai¹,

He²,

Ma³

et al. 2023

Front. Oncol.

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“…It is therefore conceivable that pol III control may provide a link between Dr1 and the proliferative and oncogenic status of mammalian cells. Dr1 expression was found to be significantly compromised in 74% of the 58 cases examined of neuroblastoma, usually due to genomic deletion ( 50 ). Little or no change in DRAP1 was detected in any of the samples ( 50 ).…”

Section: Discussionmentioning

confidence: 99%

“…Dr1 expression was found to be significantly compromised in 74% of the 58 cases examined of neuroblastoma, usually due to genomic deletion ( 50 ). Little or no change in DRAP1 was detected in any of the samples ( 50 ). Our data suggest that the reduced Dr1 levels in these early childhood tumours may result in elevated tRNA expression.…”

Section: Discussionmentioning

confidence: 99%

Dr1 (NC2) is present at tRNA genes and represses their transcription in human cells

Kantidakis¹,

White²

2009

Nucleic Acids Research

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Dr1 (also known as NC2β) was identified as a repressor of RNA polymerase (pol) II transcription. It was subsequently shown to inhibit pol III transcription when expressed at high levels in vitro or in yeast cells. However, endogenous Dr1 was not detected at pol III-transcribed genes in growing yeast. In contrast, we demonstrate that endogenous Dr1 is present at pol III templates in human cells, as is its dimerization partner DRAP1 (also called NC2α). Expression of tRNA by pol III is selectively enhanced by RNAi-mediated depletion of endogenous human Dr1, but we found no evidence that DRAP1 influences pol III output in vivo. A stable association was detected between endogenous Dr1 and the pol III-specific transcription factor Brf1. This interaction may recruit Dr1 to pol III templates in vivo, as crosslinking to these sites increases following Brf1 induction. On the basis of these data, we conclude that the physiological functions of human Dr1 include regulation of pol III transcription.

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MIR152, MIR200B, and MIR338, human positional and functional neuroblastoma candidates, are involved in neuroblast differentiation and apoptosis

et al. 2010

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MicroRNAs (MIRs) perform critical regulatory functions within cell networks, both in physiology as well as in pathology. Through the positional gene candidate approach, we have identified three MIRs (MIR152, MIR200B, and MIR338) that are located in regions frequently altered in neuroblastoma (NB) and target mRNAs encoding proteins involved in cell proliferation, neuroblast differentiation, neuroblast migration, and apoptosis. Expression analysis in NB biopsies and NB cell lines showed that these MIRs are dysregulated. We have characterized a CpG island, close to the gene encoding MIR200B and hypermethylated in NB samples, that explains its negative regulation. Expression of MIR152, MIR200B, and MIR338 is specifically modulated in NB cell lines during differentiation and apoptosis. Functional genomic experiments through enforced expression of MIR200B and knockdown of MIR152 resulted in a significant decrease of the invasion activity of SH-SY5Y cells. Reconstruction of a NB network comprising MIR152, MIR200B, and MIR338 allowed us to confirm their role in the control of NB cell stemness and apoptosis: This suggests that altered regulation of these MIRs could have a role in NB pathogenesis by interfering with the molecular mechanisms, which physiologically control differentiation and death of neuroblasts. Accordingly, they could be considered as new NB biomarkers and potential targets of antagomirs or epigenetic therapies.

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Involvement of GTA protein NC2β in Neuroblastoma pathogenesis suggests that it physiologically participates in the regulation of cell proliferation

Cited by 5 publications

References 46 publications

Identification of DNA repair gene signature and potential molecular subtypes in hepatocellular carcinoma

Identification of DNA repair gene signature and potential molecular subtypes in hepatocellular carcinoma

Dr1 (NC2) is present at tRNA genes and represses their transcription in human cells

MIR152, MIR200B, and MIR338, human positional and functional neuroblastoma candidates, are involved in neuroblast differentiation and apoptosis

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