FOXQ1 regulates senescence-associated inflammation via activation of SIRT1 expression

Wang, Pan; Lv, Cuicui; Zhang, Tao; Liu, Junling; Yang, Jin; Guan, Fangxia; Hong, Tianpei

doi:10.1038/cddis.2017.340

Cited by 31 publications

(24 citation statements)

References 37 publications

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“…SIRT1 is the most widely studied member of the SIRT family and is known to modulate cell proliferation, differentiation, apoptosis, migration and invasion ( 3 , 7 , 28 ). SIRT1 controls cellular senescence and is overexpressed in specific cancer cell types ( 29 , 30 ). In the present study, the effect of 15d-PGJ 2 and its derivatives on SIRT1-mediated cell death pathways were investigated in SKOV3 cells.…”

Section: Discussionmentioning

confidence: 99%

Novel SIRT1 inhibitor 15-deoxy-Δ12,14-prostaglandin J2 and its derivatives exhibit anticancer activity through apoptotic or autophagic cell death pathways in SKOV3 cells

et al. 2018

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Clinically relevant sirtuin (SIRT) inhibitors may possess antitumor activities. A previous study indicated that 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) exhibited potent anticancer activity by SIRT1 inhibition. Therefore, the aim of the present study was to investigate whether its derivatives (J11-C1 and J19) exhibited anticancer activity against ovarian cancer SKOV3 cells. Cell viability was determined using an MTT assay. Cell cycle arrest, apoptosis and autophagy were determined using flow cytometry or western blot analysis. J11-Cl and J19 were less cytotoxic to SKOV3 cells compared with 15d-PGJ2. Molecular docking studies supported the interactions of 15d-PGJ2, J11-Cl and J19 with various amino acids in SIRT1 proteins. Similar to 15d-PGJ2, J11-C1 and J19 inhibited SIRT1 enzymatic activity and decreased SIRT1 expression levels in a concentration-dependent manner. J11-C1 induced apoptotic cell death more effectively compared with J19, which was associated with markedly decreased expression of the anti-apoptotic molecule B-cell lymphoma 2 (Bcl-2). Furthermore, the levels of light chain 3-II (LC3-II) and beclin-1 were clearly induced in SKOV3 cells treated with J11-Cl. Thus, 15d-PGJ2 and its derivatives exhibited anticancer activity possibly by inducing apoptotic or autophagic cell death pathways. Collectively, the results of the present study suggest that 15d-PGJ2 and its derivatives exerted antitumor activity by selectively modulating the expression of genes associated with cell cycle arrest, apoptosis and autophagy. Notably, J11-C1 is a novel candidate SIRT1 inhibitor with anticancer activity.

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Section: Discussionmentioning

confidence: 99%

Novel SIRT1 inhibitor 15-deoxy-Δ12,14-prostaglandin J2 and its derivatives exhibit anticancer activity through apoptotic or autophagic cell death pathways in SKOV3 cells

et al. 2018

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“…Then, we used a selective SIRT1 inhibitor, Selisistat (EX-27) [29,30], to test whether SAL-induced mitochondrial biogenesis is dependent on SIRT1 activation. According to the previous studies [30,31] and our pilot studies, EX-527 at 10 μM was used to inhibit SIRT1 activity and did not cause cell death in 2BS fibroblasts. It was added to the medium 2 h earlier before the SAL or RES treatment and was present until cell harvest.…”

Section: Sal Stimulates Mitochondrial Biogenesismentioning

confidence: 99%

Salidroside Delays Cellular Senescence by Stimulating Mitochondrial Biogenesis Partly through a miR-22/SIRT-1 Pathway

Mao

Wang

et al. 2019

Oxidative Medicine and Cellular Longevity

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Calorie restriction (CR) is a nongenetic intervention with a robust effect on delaying aging in mammals and other organisms. A mild stimulation on mitochondrial biogenesis induced by CR seems to be an important action mode for its benefits. Here, we reported that a component isolated from Rhodiola rosea L., salidroside, delays replicative senescence in human fibroblasts, which is related to its stimulation on mitochondrial biogenesis by activating SIRT1 partly resulted from inhibition on miR-22. Salidroside increased the mitochondrial mass that accompanied an increment of the key regulators of mitochondrial biogenesis including PGC-1α, NRF-1, and TFAM and reversed the mitochondrial dysfunction in presenescent 50PD cells, showing a comparable effect to that of resveratrol. SIRT1 is involved in the inducement of mitochondrial biogenesis by salidroside. The declined expression of SIRT1 in 50PD cells compared with the young 30PD cells was prevented upon salidroside treatment. In addition, pretreatment of EX-527, a selective SIRT1 inhibitor, could block the increased mitochondrial mass and decreased ROS production induced by salidroside in 50PD cells, resulting in an accelerated cellular senescence. We further found that salidroside reversed the elevated miR-22 expression in presenescent cells according to a miRNA array analysis and a subsequent qPCR validation. Enforced miR-22 expression by using a Pre-miR-22 lentiviral construct induced the young fibroblasts (30PD) into a senescence state, accompanied with increased senescence-related molecules including p53, p21, p16, and decreased SIRT1 expression, a known target of miR-22. However, salidroside could partly impede the senescence progression induced by lenti-Pre-miR-22. Taken together, our data suggest that salidroside delays replicative senescence by stimulating mitochondrial biogenesis partly through a miR22/SIRT1 pathway, which enriches our current knowledge of a salidroside-mediated postpone senility effect and provides a new perspective on the antidecrepitude function of this naturally occurring compound in animals and humans.

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“…FOXQ1 is a member of the forkhead-box (FOX) transcription factor gene family, which contains a winged helix DNA binding domain and has important functions in development, cancer, aging, cell cycle regulation, cell migration, and other diverse cellular processes [ 1 – 5 ]. Previous studies in mammals show that the functions of FOXQ1 include promoting epithelial differentiation [ 6 – 11 ], inhibiting smooth muscle differentiation [ 12 ], mediating hair development [ 13 , 14 ], controlling gastric acid production and secretion in stomach mucous cells [ 15 , 16 ], regulating glucose metabolism [ 17 ], as well as possible immunological functions [ 18 , 19 ]. Additionally, upregulation of FOXQ1 is found in a large host of cancer types, possibly to regulate cell proliferation and invasion, including breast [ 7 , 20 , 21 ], colorectal [ 22 – 25 ], pancreatic [ 26 , 27 ], gastric [ 28 – 31 ], bladder [ 32 ], liver [ 33 – 36 ], lung [ 37 , 38 ], ovarian [ 39 , 40 ], and glioma [ 41 ].…”

Section: Introductionmentioning

confidence: 99%

Genetic analysis of zebrafish homologs of human FOXQ1, foxq1a and foxq1b, in innate immune cell development and bacterial host response

2018

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FOXQ1 is a member of the forkhead-box transcription factor family that has important functions in development, cancer, aging, and many cellular processes. The role of FOXQ1 in cancer biology has raised intense interest, yet much remains poorly understood. We investigated the possible function of the two zebrafish orthologs (foxq1a and foxq1b) of human FOXQ1 in innate immune cell development and function. We employed CRISPR-Cas9 targeted mutagenesis to create null mutations of foxq1a and foxq1b in zebrafish. Using a combination of molecular, cellular, and embryological approaches, we characterized single and double foxq1a bcz11 and foxq1b bcz18 mutants. This study provides the first genetic mutant analyses of zebrafish foxq1a and foxq1b. Interestingly, we found that foxq1a, but not foxq1b, was transcriptionally regulated during a bacterial response, while the expression of foxq1a was detected in sorted macrophages and upregulated in foxq1a-deficient mutants. However, the transcriptional response to E. coli challenge of foxq1a and foxq1b mutants was not significantly different from that of their wildtype control siblings. Our data shows that foxq1a may have a role in modulating bacterial response, while both foxq1a and foxq1b are not required for the development of macrophages, neutrophils, and microglia. Considering the implicated role of FOXQ1 in a vast number of cancers and biological processes, the foxq1a and foxq1b null mutants from this study provide useful genetic models to further investigate FOXQ1 functions.

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FOXQ1 regulates senescence-associated inflammation via activation of SIRT1 expression

Cited by 31 publications

References 37 publications

Novel SIRT1 inhibitor 15-deoxy-Δ12,14-prostaglandin J2 and its derivatives exhibit anticancer activity through apoptotic or autophagic cell death pathways in SKOV3 cells

Novel SIRT1 inhibitor 15-deoxy-Δ12,14-prostaglandin J2 and its derivatives exhibit anticancer activity through apoptotic or autophagic cell death pathways in SKOV3 cells

Salidroside Delays Cellular Senescence by Stimulating Mitochondrial Biogenesis Partly through a miR-22/SIRT-1 Pathway

Genetic analysis of zebrafish homologs of human FOXQ1, foxq1a and foxq1b, in innate immune cell development and bacterial host response

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