SIRT3, a metabolic target linked to ataxia-telangiectasia mutated (ATM) gene deficiency in diffuse large B-cell lymphoma

Bhalla, Kavita; Jaber, Sausan; Reagan, Kayla; Hamburg, Arielle; Underwood, Karen; Jhajharia, Aditya; Singh, Montek; Bhat, Shambhu; Nanaji, Nahid; Hisa, Ruching; McCracken, Carrie; Creasy, Heather Huot; Lapidus, Rena G.; Kingsbury, Tami J.; Mayer, Dirk; Polster, Brian M.; Gartenhaus, Ronald B.

doi:10.1038/s41598-020-78193-6

Cited by 10 publications

(3 citation statements)

References 71 publications

(96 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Studies have reported the increased dependence on glutaminolysis in cancer cells [ 65 , 66 ] and neurons [ 67 ] with mitochondrial defects and high metabolic demands. In response to energy crisis or high anabolic demand, cells could cause an adaptive upregulation of glutaminolysis as a compensatory response [ 68 , 69 ] to support the TCA cycle, providing reducing equivalent for oxidative phosphorylation or providing carbon source for biosynthesis [ 24 , 70 ].…”

Section: Discussionmentioning

confidence: 99%

Glutaminolysis regulates endometrial fibrosis in intrauterine adhesion via modulating mitochondrial function

Chen,

Ye,

Huang

et al. 2024

Biol Res

View full text Add to dashboard Cite

Background Endometrial fibrosis, a significant characteristic of intrauterine adhesion (IUA), is caused by the excessive differentiation and activation of endometrial stromal cells (ESCs). Glutaminolysis is the metabolic process of glutamine (Gln), which has been implicated in multiple types of organ fibrosis. So far, little is known about whether glutaminolysis plays a role in endometrial fibrosis. Methods The activation model of ESCs was constructed by TGF-β1, followed by RNA-sequencing analysis. Changes in glutaminase1 (GLS1) expression at RNA and protein levels in activated ESCs were verified experimentally. Human IUA samples were collected to verify GLS1 expression in endometrial fibrosis. GLS1 inhibitor and glutamine deprivation were applied to ESCs models to investigate the biological functions and mechanisms of glutaminolysis in ESCs activation. The IUA mice model was established to explore the effect of glutaminolysis inhibition on endometrial fibrosis. Results We found that GLS1 expression was significantly increased in activated ESCs models and fibrotic endometrium. Glutaminolysis inhibition by GLS1 inhibitor bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl) ethyl sulfide (BPTES or glutamine deprivation treatment suppressed the expression of two fibrotic markers, α-SMA and collagen I, as well as the mitochondrial function and mTORC1 signaling in ESCs. Furthermore, inhibition of the mTORC1 signaling pathway by rapamycin suppressed ESCs activation. In IUA mice models, BPTES treatment significantly ameliorated endometrial fibrosis and improved pregnancy outcomes. Conclusion Glutaminolysis and glutaminolysis-associated mTOR signaling play a role in the activation of ESCs and the pathogenesis of endometrial fibrosis through regulating mitochondrial function. Glutaminolysis inhibition suppresses the activation of ESCs, which might be a novel therapeutic strategy for IUA.

show abstract

Section: Discussionmentioning

confidence: 99%

Glutaminolysis regulates endometrial fibrosis in intrauterine adhesion via modulating mitochondrial function

Chen,

Ye,

Huang

et al. 2024

Biol Res

View full text Add to dashboard Cite

show abstract

“…Bhalla et al . 35 reported that ATM knockout induced mitochondrial deacetylase SIRT3 activity and disrupted the mitochondrial structure, thereby promoting the growth of diffuse large B-cell lymphoma. Based on these findings, ATM and p53 are two proteins that work closely together and may be involved in the construction of anti-cancer barriers.…”

Section: Discussionmentioning

confidence: 99%

miR-18a expression correlates with ATM and p53 levels and poor prognosis in lymphomas

Zhou¹,

He²,

Ou³

et al. 2023

J. Cancer

View full text Add to dashboard Cite

microRNAs (miRNAs) are non-coding, endogenous, small-molecule RNAs. They are involved in cell proliferation, differentiation, apoptosis, and metabolism. Additionally, they play an essential role in the development and progression of various malignancies. Recent research has revealed that miR-18a plays an important role in cancer development. However, its role in lymphoma is not yet fully understood. In this study, we investigated the clinicopathological characteristics and potential functional roles of miR-18a in lymphomas. First, we predicted the potential downstream genes of miR-18a using miRTarBase software and subjected these downstream genes to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses to determine the potential mechanisms of action of these genes. We found that these target genes were closely related to cellular senescence, the p53 signaling pathway, and other signaling pathways. From the predicted downstream target genes, ATM and p53 were selected as the target genes; their deletion in patients with lymphoma was detected using the fluorescence in situ hybridization technique. The results showed that some patients with lymphoma have a deletion of the ATM and p53 genes. In addition, the deletion rates of ATM and p53 were positively correlated with the expression of miR-18a. Next, the expression levels of miR-18a and the deletion rates of ATM and p53 were used for correlation and prognostic analyses with patient clinical information. The findings revealed a significant difference in disease-free survival (DFS) between patients with lymphoma with ATM deletion and those with a normal ATM gene expression ( p < 0.001). Moreover, a significant difference in overall survival (OS) and DFS between patients with p53 deletion and those with normal p53 expression was observed ( p < 0.001). The results indicate that the deletion of ATM and p53 downstream of miR-18a is closely associated with the development of lymphoma. Thus, these biomarkers may serve as key prognostic biomarkers for lymphomas.

show abstract

“…Kavita Bhalla et al 49 found elevated activity of the mitochondrial deacetylase sirtuin-3 (SIRT3) in diffuse Bcell lymphoma (DLBCL) triggered via ATM deficiency, resulting in altered mitochondrial structure, lowered TCA flux, and enrichment of the glutamate receptor and glutamine pathways. ATM kinases are vital regulators of the DNA damage response, and B-cell tumors with ATM-zero phenotype mitochondria are poorly dealt with and do no longer respond to either traditional cures or DNA damaging drugs.…”

Section: Mitochondrial Deacetylase Sirtuin-3 (Sirt3)mentioning

confidence: 99%

Application and progress of CRISPR Cas9 gene editing in B-cell lymphoma

Jin

Liu

et al. 2023

Preprint

View full text Add to dashboard Cite

In latest years, with the gradual perception of CRISPR Cas9 technology, coupled with the many advantages of the CRISPR Cas9 system, ease of development, simplicity of use, and low material prices, its mediated gene modifying has been higher used in diagnosing and treating genetic ailments and enhancing patients’ prognosis. Moreover, CRISPR Cas9 gene screening library is another hot issue which can be used to discover pathogenic genes, pick drug intervention sites, and analyze drug resistance mechanisms. Rapidly emerging gene editing technology has a huge market and is expected to cure B-cell lymphoma. This article reviews the application and progress of CRISPR Cas9 gene editing in B-cell lymphoma for further study.

show abstract

SIRT3, a metabolic target linked to ataxia-telangiectasia mutated (ATM) gene deficiency in diffuse large B-cell lymphoma

Cited by 10 publications

References 71 publications

Glutaminolysis regulates endometrial fibrosis in intrauterine adhesion via modulating mitochondrial function

Glutaminolysis regulates endometrial fibrosis in intrauterine adhesion via modulating mitochondrial function

miR-18a expression correlates with ATM and p53 levels and poor prognosis in lymphomas

Application and progress of CRISPR Cas9 gene editing in B-cell lymphoma

Contact Info

Product

Resources

About