A myeloid tumor suppressor role for <i>NOL3</i>

Stanley, Robert F.; Piszczatowski, Richard T.; Bartholdy, Boris; Mitchell, Kelly; McKimpson, Wendy M.; Narayanagari, Swathi Rao; Walter, Dagmar; Todorova, Tihomira I.; Hirsch, Cassandra M.; Makishima, Hideki; Will, Britta; McMahon, Christine M.; Gritsman, Kira; Maciejewski, Jaroslaw P.; Kitsis, Richard N.; Steidl, Ulrich

doi:10.1084/jem.20162089

Cited by 8 publications

(4 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It also limits the amount of soluble caspase-8 available for DISC-mediated activation by interacting with caspase-8 in a mitochondria localization-and phosphorylation-dependent manner. NOL3 inhibits the intrinsic apoptotic pathway in response to a wide range of stresses, via its interaction with BAX resulting in BAX inactivation, preventing mitochondrial dysfunction and pro-apoptotic factor release (Gustafsson et al 2004;Mercier et al 2008;Stanley et al 2017). The previous study demonstrates that transduced NOL3 protein protected against oxidative stress-induced cell death by inhibiting the intrinsic and extrinsic apoptotic pathways and suggests that transduced NOL3 protein inhibited H 2 O 2induced neuronal cell death through the regulation of apoptotic signal pathways (Eun et al 2016).…”

Section: Discussionmentioning

confidence: 99%

The synergistic antitumour effect of multi-components from Pulsatilla chinensis saponins in NCI-H460 lung cancer cell line through induction of apoptosis

Guan

Chen

Zhou

et al. 2020

Pharmaceutical Biology

View full text Add to dashboard Cite

Context: Pulsatilla chinensis (Bunge) Regel (Ranunculaceae) possess antitumour effects; however, its antitumour potential has not been extensively investigated. Objective: To investigate the synergetic effect of multi-components from P. chinensis induced cell apoptosis and explore the mechanism. Materials and methods: The cytotoxicity was measured against NCI-H460, SMMC-7721, HCT-116 and U251 cell lines treated with eight monomers from P. chinensis. The synergetic effect of a combination of Pulsatilla saponin D (PSD), Raddeanoside R13 (R13), and Pulsatilla saponin A (PSA) was assessed using CalcuSyn3.0. Annexin V-FITC/PI and DAPI staining analyzed apoptosis of NCI-H460 cells treated with PSD, R13 and PSA alone or in combination. Proteins differential expression was analyzed using proteomic, DAVID Bioinformatics Resources, R software environment and KEGG database, and verified by western blotting. Results: PSD, R13, and PSA displayed greater antitumor activity with IC 50 values of 5.6, 5.1 and 10.5 mM against NCI-H460 cells compared with other monomers. The combination of PSD, R13, and PSA had a synergistic effect at CI ¼ 0.27 and induced 17.53% cells apoptotic detected by flow cytometric. Bioinformatic analysis showed an overview of the differentially expressed proteins and some signalling pathways. Moreover, some candidate proteins (LDHA, PI3K, NOL3 and cleaved-caspase-3) were validated by western blotting. Discussion and Conclusion: These results show PSD, R13, and PSA are good candidates as natural products for use in the treatment of lung cancer. Potential signalling pathways and protein targets need to be further validated. The application of the drug combination approach also provides a therapeutic strategy for cancer.

show abstract

Section: Discussionmentioning

confidence: 99%

The synergistic antitumour effect of multi-components from Pulsatilla chinensis saponins in NCI-H460 lung cancer cell line through induction of apoptosis

Guan

Chen

Zhou

et al. 2020

Pharmaceutical Biology

View full text Add to dashboard Cite

show abstract

“…It was found that NOL3 has very different expression levels between the wildtype and the diabetic kidneys ( Figure 3 A). The NOL3 protein, also known as Apoptosis Repressor with CARD Domain (ARC), is involved in inhibiting apoptosis, or programmed cell death, and is expressed in a variety of human tissues [ 30 , 31 ]. The reconstructed images displaying NOL3 expression on MIST arrays reveal distributions and levels of expression that are consistent with those observed in the immunostained tissue images.…”

Section: Resultsmentioning

confidence: 99%

Single-Cell Spatial MIST for Versatile, Scalable Detection of Protein Markers

Meah,

Vedarethinam,

Bronstein

et al. 2023

Biosensors

View full text Add to dashboard Cite

High-multiplex detection of protein biomarkers across tissue regions has been an attractive spatial biology approach due to significant advantages over traditional immunohistochemistry (IHC) methods. Different from most methods, spatial multiplex in situ tagging (MIST) transfers the spatial protein expression information to an ultrahigh-density, large-scale MIST array. This technique has been optimized to reach single-cell resolution by adoption of smaller array units and 30% 8-arm PEG polymer as transfer medium. Tissue cell nuclei stained with lamin B have been clearly visualized on the MIST arrays and are colocalized with detection of nine mouse brain markers. Pseudocells defined at 10 μm in size have been used to fully profile tissue regions including cells and the intercellular space. We showcased the versatility of our technology by successfully detecting 20 marker proteins in kidney samples with the addition of five minutes atop the duration of standard immunohistochemistry protocols. Spatial MIST is amenable to iterative staining and detection on the same tissue samples. When 25 proteins were co-detected on 1 mouse brain section for each round and 5 rounds were executed, an ultrahigh multiplexity of 125 proteins was obtained for each pseudocell. With its unique abilities, this single-cell spatial MIST technology has the potential to become an important method in advanced diagnosis of complex diseases.

show abstract

“…NOL3 is also known as an apoptosis repressor with a caspase recruitment domain (ARC), it potentially antagonizes apoptosis pathways to inhibit cell death (30). Increased expression of NOL3 is shown in solid tumors and mediate cellular responsiveness to pharmacologic apoptosis induction (31). But a study held the view that NOL3 was decreased in the majority of ccRCC and decreased NOL3 conferred resistance to sunitinib in vitro, which are contradictory to available researches (32).…”

Section: Discussionmentioning

confidence: 99%

Discovery and construction of prognostic model for clear cell renal cell carcinoma based on single-cell and bulk transcriptome analysis

Zhang¹,

Yu²,

Wu³

et al. 2021

Transl Androl Urol

View full text Add to dashboard Cite

Background: Clear cell renal cell carcinoma (ccRCC) is the most common malignant kidney tumor in adults. Single-cell transcriptome sequencing can provide accurate gene expression data of individual cells.Integrated single-cell and bulk transcriptome data from ccRCC samples provide comprehensive information, which allows the discovery of new understandings of ccRCC and the construction of a novel prognostic model for ccRCC patients.Methods: Single-cell transcriptome sequencing data was preprocessed by using the Seurat package in R software. Principal component analysis (PCA) and the t-distributed stochastic neighbor embedding (t-SNE) algorithm were used to perform cluster classification. Two subtypes of cancer cells were identified, pseudotime trajectory analysis and gene ontology (GO) analysis were conducted with the monocle and clusterProfiler packages. Two novel cancer cell biomarkers were identified according to the single-cell sequencing and were confirmed by The Cancer Genome Atlas (TCGA) data. T cell-related marker genes according to single-cell sequencing were screened by a combination of Kaplan-Meier (KM) analysis, univariate Cox analysis, least absolute shrinkage and selection operator (Lasso) regression and multivariate Cox analysis of TCGA data. Four survival predicting genes were screened out to develop a risk score model.A nomogram consisting of the risk score and clinical information was constructed to predict the prognosis for ccRCC patients.Results: A total of 5,933 cells were included in the study after quality control. Fifteen cell clusters were classified by PCA and t-SNE algorithm. Two clusters of cancer cells with distinct differentiation status were identified. Besides, GO analysis revealed that biological processes were different between the two subgroups.Egl-9 family hypoxia-inducible factor 3 (EGLN3) and nucleolar protein 3 (NOL3) were specifically expressed in cancer cell clusters, bulk RNA sequencing data from TCGA confirmed their high expression in ccRCC tissues. GTSE1, CENPF, SMC2 and H2AFV were screened out and applied to the construction of risk score model. A nomogram was generated to predict prognosis of ccRCC by combing the risk score and clinical parameters. Conclusions: We integrated single-cell and bulk transcriptome data from ccRCC in this study. Two subtypes of ccRCC cells with different biological characteristics and two potential biomarkers of ccRCC were discovered. A novel prognostic model was constructed for clinical application. 2 Zhang et al. A novel prognostic nomogram for ccRCC

show abstract

A myeloid tumor suppressor role for NOL3

Cited by 8 publications

References 60 publications

The synergistic antitumour effect of multi-components from Pulsatilla chinensis saponins in NCI-H460 lung cancer cell line through induction of apoptosis

The synergistic antitumour effect of multi-components from Pulsatilla chinensis saponins in NCI-H460 lung cancer cell line through induction of apoptosis

Single-Cell Spatial MIST for Versatile, Scalable Detection of Protein Markers

Discovery and construction of prognostic model for clear cell renal cell carcinoma based on single-cell and bulk transcriptome analysis

Contact Info

Product

Resources

About