Nuclear Respiratory Factor 1 (NRF1) Transcriptional Activity-Driven Gene Signature Association with Severity of Astrocytoma and Poor Prognosis of Glioblastoma

Bhawe, Kaumudi; Felty, Quentin; Yoo, Changwon; Ehtesham, Nasreen Z.; Hasnain, Seyed E.; Singh, Vinod P.; Mohapatra, Ishani; Roy, Deodutta

doi:10.1007/s12035-020-01979-2

Cited by 22 publications

(18 citation statements)

References 29 publications

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“…Due to the lack of research on NBEAL2 in malignant tumors, the signi cance of NBEAL2 in other malignancy remains obscure. Interestingly, a recent study pointed out that high NBALE2 expression level may be a risk factor for poor survival of patients with IDH1 wild-type Glioblastoma(GBM), which seems contrary with our results [20]. Another research get similar conclusion with us that low NBALE2 expression level was correlated with poorer overall survival of HNSCC patients [12].…”

Section: Discussioncontrasting

confidence: 89%

Prognostic Significance of NBEAL2 in Liver hepatocellular carcinoma

Wen

Wang

et al. 2021

Preprint

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Background: NBEAL2 is a member of the BEACH domain–containing protein (BDCP) family and little is known about the relationship between NBEAL2 and malignancy.Methods: We downloaded the Gene expression profiles and clinical data of Liver hepatocellular carcinoma(LIHC) form the Cancer Genome Atlas (TCGA) dataset. The expression difference of NBEAL2 in LIHC tissues and adjacent nontumor tissues was analyzed by R software. The relationship between NBEAL2 expression and clinicopathological parameters was evaluate by Chi-square test. The effect of NBEAL2 expression on survival were assessed by Kaplan–Meier survival analysis and Cox proportional hazards regression model. GSEA was used to explore the potential molecular mechanism of NBEAL2 in LIHC.Results: Up-regulation of NBEAL2 expression was detected in the LIHC tissue compared with adjacent nontumor tissues(P < 0.001). The chi-square test showed that no significant correlation between the expression level of NBEAL2 and various clinicopathological parameters (including T, N and M classifications) were detected. The Kaplan–Meier curves suggested that lower NBEAL2 expression was related with poor prognosis. The results of Multivariate analysis revealed that a lower expression of NBEAL2 in LIHC was an independent risk of poor overall survival (HR, 8.873; 95% CI, 1.159-67.936; P = 0.035). GSEA suggested that multiple tumor-related metabolic pathways were evidently enriched in samples with the low-NBEAL2 expression phenotype. Conlusion: NBEAL2 might act as an tumor suppressor gene in the progression of LIHC but the precise role of NBELA2 in LIHC needs further vertification.

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Section: Discussioncontrasting

confidence: 89%

Prognostic Significance of NBEAL2 in Liver hepatocellular carcinoma

Wen

Wang

et al. 2021

Preprint

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“…Overall, ARMC5 plays a key role in regulating cell cycle progression. This finding is in accordance with the result that nuclear respiratory factor 1 (NRF1), a transcription factor, is highly active in astrocytoma and can indirectly regulate the cell cycle by targeting ARMC5 to promote glioma proliferation ( Bhawe et al, 2020 ). The finding also illustrates why the knockout of ARMC5 inhibits T cell proliferation and differentiation into TH1 and TH17 cells and increases T cell apoptosis ( Hu et al, 2017 ) and why ARMC5 mutations may cause meningioma ( Elbelt et al, 2015 ).…”

Section: Functional Interactions Of the Armc Subfamily In Specific Diseasessupporting

confidence: 91%

ARMC Subfamily: Structures, Functions, Evolutions, Interactions, and Diseases

Huang

Jiang

Gao

et al. 2021

Front. Mol. Biosci.

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Armadillo repeat-containing proteins (ARMCs) are widely distributed in eukaryotes and have important influences on cell adhesion, signal transduction, mitochondrial function regulation, tumorigenesis, and other processes. These proteins share a similar domain consisting of tandem repeats approximately 42 amino acids in length, and this domain constitutes a substantial platform for the binding between ARMCs and other proteins. An ARMC subfamily, including ARMC1∼10, ARMC12, and ARMCX1∼6, has received increasing attention. These proteins may have many terminal regions and play a critical role in various diseases. On the one hand, based on their similar central domain of tandem repeats, this ARMC subfamily may function similarly to other ARMCs. On the other hand, the unique domains on their terminals may cause these proteins to have different functions. Here, we focus on the ARMC subfamily (ARMC1∼10, ARMC12, and ARMCX1∼6), which is relatively conserved in vertebrates and highly conserved in mammals, particularly primates. We review the structures, biological functions, evolutions, interactions, and related diseases of the ARMC subfamily, which involve more than 30 diseases and 40 bypasses, including interactions and relationships between more than 100 proteins and signaling molecules. We look forward to obtaining a clearer understanding of the ARMC subfamily to facilitate further in-depth research and treatment of related diseases.

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“…In addition, the transcription factor activity of NRF1 is highly active in human cancer. Recently, Bhawe et al reported that aberrant NRF1 activity and its regulated genes, including TGF-β1 and p15INK4b, are overexpressed in glioblastoma (high-grade astrocytoma) [ 15 ]. p15INK4b, an E2F target gene, also functions as a downstream effector of SMAD4-mediated antiproliferative effects.…”

Section: Discussionmentioning

confidence: 99%

“…Besides its role in the regulation of mitochondrial functions, NRF1 is also a crucial player in histone gene expression and acts as a regulator of cell growth and proliferation [ 13 , 14 ]. Accumulating evidences also implicate that NRF1 expression and its transcription factor activity may contribute to the pathogenesis of breast cancer, glioblastoma, and neuronal dysfunction [ 15 , 16 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

Nuclear Respiratory Factor-1, a Novel SMAD4 Binding Protein, Represses TGF-β/SMAD4 Signaling by Functioning as a Transcriptional Cofactor

Rajasekaran

Song

Lee

et al. 2021

IJMS

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SMAD4, a key regulator of transforming growth factor-β (TGF-β) signaling, plays a major role in cell growth, migration, and apoptosis. In particular, TGF-β/SMAD induces growth arrest, and SMAD4 induces the expression of target genes such as p21WAF1 and p15INK4b through its interaction with several cofactors. Thus, inactivating mutations or the homozygous deletion of SMAD4 could be related to tumorigenesis or malignancy progression. However, in some cancer types, SMAD4 is neither mutated nor deleted. In the current study, we demonstrate that TGF-β signaling with a preserved SMAD4 function can contribute to cancer through associations with negative pathway regulators. We found that nuclear respiratory factor-1 (NRF1) is a novel interaction SMAD4 partner that inhibits TGF-β/SMAD4-induced p15INK4b mRNA expression by binding to SMAD4. Furthermore, we confirmed that NRF1 directly binds to the core region of the SMAD4 promoter, thereby decreasing SMAD4 mRNA expression. On the whole, our data suggest that NRF1 is a negative regulator of SMAD4 and can interfere with TGF-β/SMAD-induced tumor suppression. Our findings provide a novel perception into the molecular basis of TGF-β/SMAD4-signaling suppression in tumorigenesis.

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Nuclear Respiratory Factor 1 (NRF1) Transcriptional Activity-Driven Gene Signature Association with Severity of Astrocytoma and Poor Prognosis of Glioblastoma

Cited by 22 publications

References 29 publications

Prognostic Significance of NBEAL2 in Liver hepatocellular carcinoma

Prognostic Significance of NBEAL2 in Liver hepatocellular carcinoma

ARMC Subfamily: Structures, Functions, Evolutions, Interactions, and Diseases

Nuclear Respiratory Factor-1, a Novel SMAD4 Binding Protein, Represses TGF-β/SMAD4 Signaling by Functioning as a Transcriptional Cofactor

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