SIRT1 suppresses the migration and invasion of gastric cancer by regulating ARHGAP5 expression.


:Gastric cancer (GC) ranks among the top five malignant tumors worldwide by the incidence and mortality rate. However, the mechanisms underlying its progression are poorly understood. In this study, we investigated the role of SIRT1, a class III deacetylase, in the invasion and metastasis of GC. Here, we found that knockdown of SIRT1 promoted GC cell migration and invasion in vitro and metastasis in vivo. Forced expression of SIRT1 in GC cells had the opposite effects. Then, we used mRNA microarray to identify the target genes that are regulated by SIRT1 and found that ARHGAP5 was downregulated by SIRT1. The results of the mRNA microarray were confirmed in several GC cell lines. Furthermore, SIRT1 inhibited the expression of ARHGAP5 by physically associating with transcription factor c-JUN and deacetylating and inhibiting the transcriptional activity of c-JUN. Then the expression dynamics and clinical significance of ARHGAP5 were analyzed using clinical samples and database. The expression of ARHGAP5 was increased in GC, and positively correlated with tumor size, tumor infiltration, lymph node metastasis, and clinical stage. And multivariate analyses indicated that ARHGAP5 served as an independent prognostic marker of GC. In addition, the biological effects of ARHGAP5 in SIRT1-mediated inhibition of GC migration and invasion were investigated using both in vitro and in vivo models. Silencing of ARHGAP5 considerably inhibited the migration and invasion of GC, and ARHGAP5 was found to be involved in the SIRT1-mediated inhibition of GC migration and invasion. Our results indicate that SIRT1 suppresses migration and invasion of GC by downregulating ARHGAP5 through an interaction with c-JUN, and these phenomena represent a novel mechanism of the antitumor action of SIRT1.


Cell Death Dis


Cell death & disease


Dong G,Wang B,An Y,Li J,Wang X,Jia J,Yang Q




Has Abstract


2018-09-24 00:00:00












  • Holliday junction recognition protein promotes pancreatic cancer growth and metastasis via modulation of the MDM2/p53 signaling.

    abstract::Holliday junction recognition protein (HJURP) refers to a histone H3 chaperone that has been implicated in different kinds of malignancies. Yet, its character in pancreatic cancer remains unclear. The expression of HJURP was assessed in PDAC tissues by RT-qPCR, immunoblotting, and immunohistochemistry. HJURP-deficient...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Wang CJ,Li X,Shi P,Ding HY,Liu YP,Li T,Lin PP,Wang YS,Zhang GQ,Cao Y

    更新日期:2020-05-21 00:00:00

  • Renal inhibition of miR-181a ameliorates 5-fluorouracil-induced mesangial cell apoptosis and nephrotoxicity.

    abstract::The development of nephrotoxicity largely limits the clinical use of chemotherapy. MiRNAs are able to target various genes and involved in the regulation of diverse cellular processes, including cell apoptosis and death. Our study showed that miR-181a expression was significantly increased after 5-fluorouracil (5-FU) ...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Liu XY,Zhang FR,Shang JY,Liu YY,Lv XF,Yuan JN,Zhang TT,Li K,Lin XC,Liu X,Lei Q,Fu XD,Zhou JG,Liang SJ

    更新日期:2018-05-23 00:00:00

  • Glucolipotoxicity initiates pancreatic β-cell death through TNFR5/CD40-mediated STAT1 and NF-κB activation.

    abstract::Type 2 diabetes is a chronic metabolic disorder, where failure to maintain normal glucose homoeostasis is associated with, and exacerbated by, obesity and the concomitant-elevated free fatty acid concentrations typically found in these patients. Hyperglycaemia and hyperlipidaemia together contribute to a decline in in...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Bagnati M,Ogunkolade BW,Marshall C,Tucci C,Hanna K,Jones TA,Bugliani M,Nedjai B,Caton PW,Kieswich J,Yaqoob MM,Ball GR,Marchetti P,Hitman GA,Turner MD

    更新日期:2016-08-11 00:00:00

  • Correction: Mechanism of Snhg8/miR-384/Hoxa13/FAM3A axis regulating neuronal apoptosis in ischemic mice model.

    abstract::Following the publication of this article, the authors realized there was an error in Figure 6H in which two versions of the figure appear.This does not impact the conclusions of the article. ...

    journal_title:Cell death & disease

    pub_type: 已发布勘误


    authors: Liu J,An P,Xue Y,Che D,Liu X,Zheng J,Liu Y,Yang C,Li Z,Yu B

    更新日期:2019-08-21 00:00:00

  • MiR-22 suppresses epithelial-mesenchymal transition in bladder cancer by inhibiting Snail and MAPK1/Slug/vimentin feedback loop.

    abstract::MicroRNAs (miRNAs) have been validated to play prominent roles in the occurrence and development of bladder cancer (BCa). MiR-22 was previously reported to act as a tumor suppressor or oncomiRNA in various types of cancer. However, its accurate expression, function, and mechanism in BCa remain unclear. Here, we find t...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Xu M,Li J,Wang X,Meng S,Shen J,Wang S,Xu X,Xie B,Liu B,Xie L

    更新日期:2018-02-12 00:00:00

  • Release and activity of histone in diseases.

    abstract::Histones and their post-translational modifications have key roles in chromatin remodeling and gene transcription. Besides intranuclear functions, histones act as damage-associated molecular pattern molecules when they are released into the extracellular space. Administration of exogenous histones to animals leads to ...

    journal_title:Cell death & disease

    pub_type: 杂志文章,评审


    authors: Chen R,Kang R,Fan XG,Tang D

    更新日期:2014-08-14 00:00:00

  • Serum amyloid A inhibits dendritic cell apoptosis to induce glucocorticoid resistance in CD4(+) T cells.

    abstract::Mediators produced by the airway epithelium control the activation, recruitment, and survival of pulmonary dendritic cells (DC) that present antigen to CD4(+) T cells during the genesis and exacerbation of allergic asthma. The epithelial-derived acute phase protein, serum amyloid A (SAA), induces DC maturation and TH1...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Ather JL,Fortner KA,Budd RC,Anathy V,Poynter ME

    更新日期:2013-09-05 00:00:00

  • Preclinical studies using cisplatin/carboplatin to restore the Enzalutamide sensitivity via degrading the androgen receptor splicing variant 7 (ARv7) to further suppress Enzalutamide resistant prostate cancer.

    abstract::The FDA-approved anti-androgen Enzalutamide (Enz) has been used successfully as the last line therapy to extend castration-resistant prostate cancer (CRPC) patients' survival by an extra 4.8 months. However, CRPC patients eventually develop Enz-resistance that may involve the induction of the androgen receptor (AR) sp...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Chou FJ,Lin C,Tian H,Lin W,You B,Lu J,Sahasrabudhe D,Huang CP,Yang V,Yeh S,Niu Y,Chang C

    更新日期:2020-11-02 00:00:00

  • Combined treatment with CBP and BET inhibitors reverses inadvertent activation of detrimental super enhancer programs in DIPG cells.

    abstract::Diffuse intrinsic pontine gliomas (DIPG) are the most aggressive brain tumors in children with 5-year survival rates of only 2%. About 85% of all DIPG are characterized by a lysine-to-methionine substitution in histone 3, which leads to global H3K27 hypomethylation accompanied by H3K27 hyperacetylation. Hyperacetylati...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Wiese M,Hamdan FH,Kubiak K,Diederichs C,Gielen GH,Nussbaumer G,Carcaboso AM,Hulleman E,Johnsen SA,Kramm CM

    更新日期:2020-08-21 00:00:00

  • Snail modulates JNK-mediated cell death in Drosophila.

    abstract::Cell death plays a pivotal role in animal development and tissue homeostasis. Dysregulation of this process is associated with a wide variety of human diseases, including developmental and immunological disorders, neurodegenerative diseases and tumors. While the fundamental role of JNK pathway in cell death has been e...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Wu C,Li Z,Ding X,Guo X,Sun Y,Wang X,Hu Y,Li T,La X,Li J,Li JA,Li W,Xue L

    更新日期:2019-11-26 00:00:00

  • miR-195 targets cyclin D3 and survivin to modulate the tumorigenesis of non-small cell lung cancer.

    abstract::miR-195 has recently been reported to function as a tumor suppressor in various cancers, including non-small cell lung cancer (NSCLC). However, the mechanisms by which miR-195 represses the tumorigenesis of NSCLC cells are not fully understood. We performed a high-throughput screen using an miRNA mimic library and con...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Yu X,Zhang Y,Cavazos D,Ma X,Zhao Z,Du L,Pertsemlidis A

    更新日期:2018-02-07 00:00:00

  • Novel ADAM-17 inhibitor ZLDI-8 enhances the in vitro and in vivo chemotherapeutic effects of Sorafenib on hepatocellular carcinoma cells.

    abstract::Hepatocellular carcinoma (HCC) is one of the greatest life threats for Chinese people, and the prognosis of this malignancy is poor due to the strong chemotherapy resistance in patients. Notch pathway components mediate cell survival and epithelial-mesenchymal transition (EMT), and also participate in the induction of...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Zhang Y,Li D,Jiang Q,Cao S,Sun H,Chai Y,Li X,Ren T,Yang R,Feng F,Li BA,Zhao Q

    更新日期:2018-07-03 00:00:00

  • The NF-κB1 is a key regulator of acute but not chronic renal injury.

    abstract::The NF-κB family of transcription factors is important for many cellular functions, in particular initiation and propagation of inflammatory and immune responses. However, recent data has suggested that different subunits of the NF-κB family can suppress the inflammatory response. NF-κB1, from the locus nfκb1, can inh...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Fearn A,Situmorang GR,Fox C,Oakley F,Howarth R,Wilson CL,Kiosia A,Robson MG,Mann DA,Moles A,Sheerin NS

    更新日期:2017-06-15 00:00:00

  • IGFBP-rP1 suppresses epithelial-mesenchymal transition and metastasis in colorectal cancer.

    abstract::Epithelial-mesenchymal transition (EMT) was initially recognized during organogenesis and has recently been reported to be involved in promoting cancer invasion and metastasis. Cooperation of transforming growth factor-β (TGF-β) and other signaling pathways, such as Ras and Wnt, is essential to inducing EMT, but the m...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Zhu S,Zhang J,Xu F,Xu E,Ruan W,Ma Y,Huang Q,Lai M

    更新日期:2015-03-19 00:00:00

  • miR4673 improves fitness profile of neoplastic cells by induction of autophagy.

    abstract::Therapeutic resistance of neoplasms is mainly attributed to gradual evolution of mutational profile1. Here, we demonstrate a microRNA-mediated mechanism that effectively improves fitness of SKBR3 mammary carcinoma cells by cytoplasmic reprogramming. The reprogramming is triggered by endogenous miR4673 transcribed from...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Dökümcü K,Simonian M,Farahani RM

    更新日期:2018-10-19 00:00:00

  • Autophagy in metabolic syndrome: breaking the wheel by targeting the renin-angiotensin system.

    abstract::Metabolic syndrome (MetS) is a complex, emerging epidemic which disrupts the metabolic homeostasis of several organs, including liver, heart, pancreas, and adipose tissue. While studies have been conducted in these research areas, the pathogenesis and mechanisms of MetS remain debatable. Lines of evidence show that ph...

    journal_title:Cell death & disease

    pub_type: 杂志文章,评审


    authors: Menikdiwela KR,Ramalingam L,Rasha F,Wang S,Dufour JM,Kalupahana NS,Sunahara KKS,Martins JO,Moustaid-Moussa N

    更新日期:2020-02-03 00:00:00

  • A novel STAT3 inhibitor attenuates angiotensin II-induced abdominal aortic aneurysm progression in mice through modulating vascular inflammation and autophagy.

    abstract::Abdominal Aortic aneurysm (AAA) is associated with chronic inflammation, cells apoptosis, and impairment of autophagy. BP-1-102, a novel potent STAT3 inhibitor, has been recently reported to significantly block inflammation-related signaling pathways of JAK2/STAT3 and NF-κB, as well as regulate autophagy. However, its...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Wu QY,Cheng Z,Zhou YZ,Zhao Y,Li JM,Zhou XM,Peng HL,Zhang GS,Liao XB,Fu XM

    更新日期:2020-02-18 00:00:00

  • Resistance to caspase-8 and -9 fragments in a malignant pleural mesothelioma cell line with acquired cisplatin-resistance.

    abstract::Apoptotic cysteine-aspartate proteases (caspases) are essential for the progression and execution of apoptosis, and detection of caspase fragmentation or activity is often used as markers of apoptosis. Cisplatin (cis-diamminedichloroplatinum (II)) is a chemotherapeutic drug that is clinically used for the treatment of...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Janson V,Johansson A,Grankvist K

    更新日期:2010-09-23 00:00:00

  • Downregulation of microRNA-383 is associated with male infertility and promotes testicular embryonal carcinoma cell proliferation by targeting IRF1.

    abstract::Our previous studies have shown that microRNA-383 (miR-383) expression is downregulated in the testes of infertile men with maturation arrest (MA). However, the underlying mechanisms of miR-383 involved in the pathogenesis of MA remain unknown. In this study, we showed that downregulation of miR-383 was associated wit...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Lian J,Tian H,Liu L,Zhang XS,Li WQ,Deng YM,Yao GD,Yin MM,Sun F

    更新日期:2010-11-04 00:00:00

  • Inhibition of cyclin-dependent kinase 4 as a potential therapeutic strategy for treatment of synovial sarcoma.

    abstract::Synovial sarcoma is a highly aggressive but rare form of soft tissue malignancy that primarily affects the extremities of the arms or legs, for which current chemotherapeutic agents have not been proven to be very effective. The cyclin-dependent kinase 4/6-retinoblastoma protein (CDK4/6-Rb) pathway of cell cycle contr...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Li X,Seebacher NA,Garbutt C,Ma H,Gao P,Xiao T,Hornicek FJ,Duan Z

    更新日期:2018-05-01 00:00:00

  • Bone marrow-derived mesenchymal stem cells ameliorate chronic high glucose-induced β-cell injury through modulation of autophagy.

    abstract::Chronic hyperglycemia causes a progressive decrease of β-cell function and mass in type 2 diabetic patients. Growing evidence suggests that augment of autophagy may be an effective approach to protect β cells against various extra-/intracellular stimuli. In this study, we thus investigated whether bone marrow-derived ...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Zhao K,Hao H,Liu J,Tong C,Cheng Y,Xie Z,Zang L,Mu Y,Han W

    更新日期:2015-09-17 00:00:00

  • Lung epithelial cell-derived extracellular vesicles activate macrophage-mediated inflammatory responses via ROCK1 pathway.

    abstract::Despite decades of research, the pathogenesis of acute respiratory distress syndrome (ARDS) remains poorly understood, thus impeding the development of effective treatment. Diffuse alveolar damage (DAD) and lung epithelial cell death are prominent features of ARDS. Lung epithelial cells are the first line of defense a...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Moon HG,Cao Y,Yang J,Lee JH,Choi HS,Jin Y

    更新日期:2015-12-10 00:00:00

  • Continuous exposure of pancreatic cancer cells to dietary bioactive agents does not induce drug resistance unlike chemotherapy.

    abstract::The repeated treatment of cancer cells with chemo- or radiotherapy induces therapy resistance, but it was previously unknown whether the same effect occurs upon continuous exposure of cancer cells to diet-derived chemopreventive agents. We elucidated this interesting question in pancreatic ductal adenocarcinoma, which...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Fan P,Zhang Y,Liu L,Zhao Z,Yin Y,Xiao X,Bauer N,Gladkich J,Mattern J,Gao C,Schemmer P,Gross W,Herr I

    更新日期:2016-06-02 00:00:00

  • Kaiso depletion attenuates the growth and survival of triple negative breast cancer cells.

    abstract::Triple negative breast cancers (TNBC) are highly aggressive and lack specific targeted therapies. Recent studies have reported high expression of the transcription factor Kaiso in triple negative tumors, and this correlates with their increased aggressiveness. However, little is known about the clinical relevance of K...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Bassey-Archibong BI,Rayner LG,Hercules SM,Aarts CW,Dvorkin-Gheva A,Bramson JL,Hassell JA,Daniel JM

    更新日期:2017-03-23 00:00:00

  • Control of glioma cell death and differentiation by PKM2-Oct4 interaction.

    abstract::Glioma stem cells are highly resistant to cell death and as such are supposed to contribute to tumor recurrence by eluding anticancer treatments. Here, we show that spheroids that contain rat neural stem cells (NSCs) or rat glioma stem cells (cancer stem cells, CSCs) express isoforms 1 and 2 of pyruvate kinase (PKM1 a...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Morfouace M,Lalier L,Oliver L,Cheray M,Pecqueur C,Cartron PF,Vallette FM

    更新日期:2014-01-30 00:00:00

  • Regulatory roles of miR-22/Redd1-mediated mitochondrial ROS and cellular autophagy in ionizing radiation-induced BMSC injury.

    abstract::Ionizing radiation (IR) response has been extensively investigated in BMSCs with an increasing consensus that this type of cells showed relative radiosensitivity in vitro analysis. However, the underlying mechanism of IR-induced injury of BMSCs has not been elucidated. In current study, the regulatory role of miR-22/R...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Liu Z,Li T,Zhu F,Deng S,Li X,He Y

    更新日期:2019-03-07 00:00:00

  • The integrity of cochlear hair cells is established and maintained through the localization of Dia1 at apical junctional complexes and stereocilia.

    abstract::Dia1, which belongs to the diaphanous-related formin family, influences a variety of cellular processes through straight actin elongation activity. Recently, novel DIA1 mutants such as p.R1213X (p.R1204X) and p.A265S, have been reported to cause an autosomal dominant sensorineural hearing loss (DFNA1). Additionally, a...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Ninoyu Y,Sakaguchi H,Lin C,Suzuki T,Hirano S,Hisa Y,Saito N,Ueyama T

    更新日期:2020-07-16 00:00:00

  • Targeting sphingosine kinase 1 (SK1) enhances oncogene-induced senescence through ceramide synthase 2 (CerS2)-mediated generation of very-long-chain ceramides.

    abstract::Senescence is an antiproliferative mechanism that can suppress tumor development and can be induced by oncogenes such as genes of the Ras family. Although studies have implicated bioactive sphingolipids (SL) in senescence, the specific mechanisms remain unclear. Here, using MCF10A mammary epithelial cells, we demonstr...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Trayssac M,Clarke CJ,Stith JL,Snider JM,Newen N,Gault CR,Hannun YA,Obeid LM

    更新日期:2021-01-04 00:00:00

  • A novel PKC activating molecule promotes neuroblast differentiation and delivery of newborn neurons in brain injuries.

    abstract::Neural stem cells are activated within neurogenic niches in response to brain injuries. This results in the production of neuroblasts, which unsuccessfully attempt to migrate toward the damaged tissue. Injuries constitute a gliogenic/non-neurogenic niche generated by the presence of anti-neurogenic signals, which impa...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Domínguez-García S,Geribaldi-Doldán N,Gómez-Oliva R,Ruiz FA,Carrascal L,Bolívar J,Verástegui C,Garcia-Alloza M,Macías-Sánchez AJ,Hernández-Galán R,Nunez-Abades P,Castro C

    更新日期:2020-04-22 00:00:00

  • Modified CAR T cells targeting membrane-proximal epitope of mesothelin enhances the antitumor function against large solid tumor.

    abstract::Mesothelin (MSLN) is an attractive antigen for chimeric antigen receptor (CAR) T therapy and the epitope selection within MSLN is essential. In this study, we constructed two types of CARs targeting either region I of MSLN (meso1 CAR, also known as a membrane-distal region) or region III of MSLN (meso3 CAR, also known...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Zhang Z,Jiang D,Yang H,He Z,Liu X,Qin W,Li L,Wang C,Li Y,Li H,Xu H,Jin H,Qian Q

    更新日期:2019-06-17 00:00:00