SIRT1 promotes proliferation, migration, and invasion of breast cancer cell line MCF-7 by upregulating DNA polymerase delta1 (POLD1)

Xu, Yan; Qin, Qinghong; Chen, Rushi; Wei, Changyuan; Mo, Qin‐Guo

doi:10.1016/j.bbrc.2018.05.164

Cited by 40 publications

(38 citation statements)

References 27 publications

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“…In addition to the anti-proliferative effects we have characterised, it should also be mentioned that p53 signalling may not be the only pathway involved in the chemopreventive activity of NSAIDs, since SIRT1 is able to modulate a variety of key targets involved in the control of apoptosis, DNA repair, inflammation, energy metabolism, angiogenesis and cell proliferation, signals that could play a significant role in the anti-cancer properties of NSAIDs. 58,59 Moreover, the increased p21 expression observed upon NSAIDs treatment might also be promoted by pathways independent from p53. 60 Future studies should address the extent to which these other signalling pathways contribute to the anti-cancer activity.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of SIRT1 deacetylase and p53 activation uncouples the anti-inflammatory and chemopreventive actions of NSAIDs

et al. 2019

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Background Nonsteroidal anti-inflammatory drugs (NSAIDs) have been proposed as chemopreventive agents for many tumours; however, the mechanism responsible for their anti-neoplastic activity remains elusive and the side effects due to cyclooxygenase (COX) inhibition prevent this clinical application. Methods Molecular biology, in silico, cellular and in vivo tools, including innovative in vivo imaging and classical biochemical assays, were applied to identify and characterise the COX-independent anti-cancer mechanism of NSAIDs. Results Here, we show that tumour-protective functions of NSAIDs and exisulind (a sulindac metabolite lacking anti-inflammatory activity) occur through a COX-independent mechanism. We demonstrate these NSAIDs counteract carcinogen-induced proliferation by inhibiting the sirtuin 1 (SIRT1) deacetylase activity, augmenting acetylation and activity of the tumour suppressor p53 and increasing the expression of the antiproliferative gene p21. These properties are shared by all NSAIDs except for ketoprofen lacking anti-cancer properties. The clinical interest of the mechanism identified is underlined by our finding that p53 is activated in mastectomy patients undergoing intraoperative ketorolac, a treatment associated with decreased relapse risk and increased survival. Conclusion Our study, for the first-time, links NSAID chemopreventive activity with direct SIRT1 inhibition and activation of the p53/p21 anti-oncogenic pathway, suggesting a novel strategy for the design of tumour-protective drugs.

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Section: Discussionmentioning

confidence: 99%

Inhibition of SIRT1 deacetylase and p53 activation uncouples the anti-inflammatory and chemopreventive actions of NSAIDs

et al. 2019

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“…SIRT is a class III histone deacetylase (HDAC), including SIRT1-SIRT7. SIRT depends on NAD+, indicating that sirtuin activity acts as a regulator for the solute ratio of NAD+/NADH cells, thus directly linking sirtuin activity to cellular metabolism and energy status [ 41 , 42 ]. SIRT1, a member of the silent information regulator 2 (Sir2) family, was reported to be involved in the occurrence and development of tumors [ 43 , 44 ].…”

Section: Discussionmentioning

confidence: 99%

Role of Sirtuin-1 in Neonatal Hypoxic-Ischemic Encephalopathy and Its Underlying Mechanism

2020

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Background Neonatal hypoxic-ischemic encephalopathy (HIE) is a dreaded disease and one of the leading causes of severe neurological dysfunction in neonates. The present study explored the functions of Sirtuin-1 (SIRT1) in neonatal HIE. Material/Methods A HIE neonatal rat model was generated to determine SIRT1 levels in brain tissues. Cell apoptosis and cell viability were analyzed by flow cytometry and MTT assay. qRT-PCR and Western blot analysis were used to assess gene mRNA and protein levels. Subsequently, the effect of SIRT1 on HIE was investigated in vitro by constructing an oxygen-glucose deprivation (OGD) cell model. Results The effective construction of the HIE rat model was confirmed by the enhanced brain cell apoptosis and the increased expression of HIE-related molecular markers, including S100 calcium-binding protein B (S100B) and neuron-specific enolase (NSE). SIRT1 expression was downregulated in HIE rat brain tissues. These findings indicated that SIRT1 was downregulated in neuronal cells subjected to OGD. In addition, enhanced cell viability and reduced cell apoptosis were observed, suggesting that SIRT1 overexpression relieved OGD-induced neuronal cell injury. Transfection with SIRT1-siRNA further increased OGD-induced neuronal cell injury, evidenced by decreased cell viability and enhanced cell apoptosis. Finally, SIRT1 overexpression significantly downregulated p-p65 protein expression. Conclusions Our findings revealed that SIRT1 may be a novel and promising therapy target for HIE treatment.

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“…Sirtuin 1 (SIRT1) is a histone deacetylase dependent on NAD + , and SIRT1-induced deacetylation of STAT3 serves a role in numerous physiological processes (21,22). Numerous studies have confirmed that SIRT1 has an important role in breast cancer (23)(24)(25). However, a novel finding suggested that SIRT1 serves a dual role in breast tumors, depending on its expression rate and the molecular subtype of the cancer (26).…”

Section: I157172 a Novel Inhibitor Of Cystathionine γ-Lyase Inhibitmentioning

confidence: 99%

I157172, a novel inhibitor of cystathionine γ-lyase, inhibits growth and migration of breast cancer cells via SIRT1-mediated deacetylation of STAT3

et al. 2018

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Cystathionine γ-lyase (CSE) is highly expressed in breast cancer, and can promote breast cancer development and progression; therefore, inhibitors of CSE may be of great significance for the treatment of breast cancer. The present study identified the CSE inhibitor I157172 through virtual screening and confirmed its activity. Subsequently, the effects and mechanism of I157172 on breast cancer cells were investigated. MTS and 5-ethynyl-2'-deoxyuridine (EdU) assays were used to assess cell viability and proliferation. Scratch wound and Transwell assays were conducted to determine cell migration and invasion. In addition, H 2 S determination was performed using the methylene blue method, and western blotting was performed to detect protein expression. The results revealed that I157172 significantly inhibited the growth, proliferation and migration of MCF7 breast cancer cells in a dose-dependent manner. The results of further mechanistic studies demonstrated that CSE expression was negatively associated with sirtuin 1 (SIRT1) in human breast cancer tissues and cells, and CSE knockdown resulted in an increase in SIRT1 expression, and a decrease in acetylated (acetyl)signal transducer and activator of transcription 3 (STAT3) and phosphorylated (p)-STAT3 levels in MCF7 cells. Furthermore, STAT3 downstream proteins B-cell lymphoma 2, p-protein kinase B, matrix metalloproteinase (MMP)-2 and MMP-9 were inhibited in CSE knockdown MCF7 cells. In addition, I157172 induced upregulation of SIRT1, and downregulation of acetyl-STAT3 and p-STAT3 (Tyr705), as well as inhibition of STAT3 downstream proteins. Taken together, I157172 inhibited the growth, proliferation and migration of breast cancer cells via upregulating SIRT1, which consequently mediated deacetylation of STAT3 and inactivation of the STAT3 pathway.

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SIRT1 promotes proliferation, migration, and invasion of breast cancer cell line MCF-7 by upregulating DNA polymerase delta1 (POLD1)

Cited by 40 publications

References 27 publications

Inhibition of SIRT1 deacetylase and p53 activation uncouples the anti-inflammatory and chemopreventive actions of NSAIDs

Inhibition of SIRT1 deacetylase and p53 activation uncouples the anti-inflammatory and chemopreventive actions of NSAIDs

Role of Sirtuin-1 in Neonatal Hypoxic-Ischemic Encephalopathy and Its Underlying Mechanism

I157172, a novel inhibitor of cystathionine γ-lyase, inhibits growth and migration of breast cancer cells via SIRT1-mediated deacetylation of STAT3

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