Suppression of SUN2 by DNA methylation is associated with HSCs activation and hepatic fibrosis.


:Hepatic myofibroblasts, activated hepatic stellate cells (HSCs), are the main cell type of extracellular matrix (ECM) deposition during hepatic fibrosis. Aberrant DNA methylation-regulated HSCs activation in liver fibrogenesis has been reported, but the functional roles and mechanisms of DNA methylation in hepatic fibrosis remain to be elucidated. In the present study, reduced representation bisulfite sequencing (RRBS) analysis of primary HSCs revealed hypermethylation patterns in hepatic fibrosis. Interestingly, we found SAD1/UNC84 domain protein-2 (SUN2) gene hypermethylation at CpG sites during liver fibrogenesis in mice with CCl4-induced hepatic fibrosis, which was accompanied by low expression of SUN2. In vivo overexpression of SUN2 following adeno-associated virus-9 (AAV9) administration inhibited CCl4-induced liver injury and reduced fibrogenesis marker expression. Consistently, in vitro experiments showed that enforced expression of SUN2 suppressed HSCs activation and exerted anti-fibrogenesis effects in TGF-β1-activated HSC-T6 cells. In addition, the signaling mechanisms related to SUN2 expression were investigated in vivo and in vitro. Methyltransferase-3b (DNMT3b) is the principal regulator of SUN2 expression. Mechanistically, inhibition of protein kinase B (AKT) phosphorylation may be a crucial pathway for SUN2-mediated HSCs activation. In conclusion, these findings provide substantial new insights into SUN2 in hepatic fibrosis.


Cell Death Dis


Cell death & disease


Chen X,Li WX,Chen Y,Li XF,Li HD,Huang HM,Bu FT,Pan XY,Yang Y,Huang C,Meng XM,Li J




Has Abstract


2018-10-03 00:00:00












  • Aquaporin 3 maintains the stemness of CD133+ hepatocellular carcinoma cells by activating STAT3.

    abstract::An increasing interest in liver cancer stemness arises owing to its aggressive behavior and poor prognosis. CD133, a widely known liver cancer stem cell marker, plays critical roles in the maintenance of liver cancer stemness. Thus, exploring the regulatory mechanism of CD133 expression is significant. In the present ...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Wang Y,Wu G,Fu X,Xu S,Wang T,Zhang Q,Yang Y

    更新日期:2019-06-13 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

  • GSK-3β-induced Tau pathology drives hippocampal neuronal cell death in Huntington's disease: involvement of astrocyte-neuron interactions.

    abstract::Glycogen synthase kinase-3β (GSK-3β) has emerged as a critical factor in several pathways involved in hippocampal neuronal maintenance and function. In Huntington's disease (HD), there are early hippocampal deficits both in patients and transgenic mouse models, which prompted us to investigate whether disease-specific...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: L'Episcopo F,Drouin-Ouellet J,Tirolo C,Pulvirenti A,Giugno R,Testa N,Caniglia S,Serapide MF,Cisbani G,Barker RA,Cicchetti F,Marchetti B

    更新日期:2016-04-28 00:00:00

  • iASPP-PP1 complex is required for cytokinetic abscission by controlling CEP55 dephosphorylation.

    abstract::Cytokinesis is the last step of cell division and is concluded by the abscission of the intercellular bridge that connects two daughter cells. The tight regulation of cytokinesis completion is essential because cytokinesis failure is associated with various human diseases. Here, we report that iASPP, a member of the a...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Gao K,Zhang Y,Shi Q,Zhang J,Zhang L,Sun H,Jiao D,Zhao X,Tao H,Wei Y,Wang Y,Saiyin H,Zhao SM,Li Y,Zhang P,Wang C

    更新日期:2018-05-01 00:00:00

  • Cell death-based treatment of glioblastoma.

    abstract::Cancer cells including glioblastoma have typically evolved multiple mechanisms to escape programmed cell death in order to maintain their survival. Defects in cell death mechanisms not only facilitate tumorigenesis but also ensure resistance to current anticancer therapies. This emphasizes that targeting cell death pa...

    journal_title:Cell death & disease

    pub_type: 杂志文章,评审


    authors: Fulda S

    更新日期:2018-01-25 00:00:00

  • Correction to: Disease-linked connexin26 S17F promotes volar skin abnormalities and mild wound healing defects in mice.

    abstract::Correction to: NPG Asia Materials (2018) published online on 16 April 2018. ...

    journal_title:Cell death & disease

    pub_type: 已发布勘误


    authors: Press E,Alaga KC,Barr K,Shao Q,Bosen F,Willecke K,Laird DW

    更新日期:2018-05-24 00:00:00

  • Dissecting cell diversity and connectivity in skeletal muscle for myogenesis.

    abstract::Characterized by their slow adhering property, skeletal muscle myogenic progenitor cells (MPCs) have been widely utilized in skeletal muscle tissue engineering for muscle regeneration, but with limited efficacy. Skeletal muscle regeneration is regulated by various cell types, including a large number of rapidly adheri...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Liu YX,Wu BB,Gong L,An CR,Lin JX,Li QK,Jiang DM,Jin KX,Mechakra A,Bunpetch V,Li Y,Zou YW,Ouyang HW,Zou XH

    更新日期:2019-06-03 00:00:00

  • Akt inhibitor SC66 promotes cell sensitivity to cisplatin in chemoresistant ovarian cancer cells through inhibition of COL11A1 expression.

    abstract::We studied Akt inhibition using SC66 in a NOD-SCID xenograft mouse model and a panel of eight ovarian cancer cell lines. Elevated phospho-Akt levels in cancerous tissue were associated with short progression-free survival and overall survival. Cell sensitivity to SC66 was inversely correlated with phospho-Akt and COL1...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Wu YH,Huang YF,Chen CC,Chou CY

    更新日期:2019-04-11 00:00:00

  • Age-severity matched cytokine profiling reveals specific signatures in Covid-19 patients.

    abstract::A global effort is currently undertaken to restrain the COVID-19 pandemic. Host immunity has come out as a determinant for COVID-19 clinical outcomes, and several studies investigated the immune profiling of SARS-CoV-2 infected people to properly direct the clinical management of the disease. Thus, lymphopenia, T-cell...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Angioni R,Sánchez-Rodríguez R,Munari F,Bertoldi N,Arcidiacono D,Cavinato S,Marturano D,Zaramella A,Realdon S,Cattelan A,Viola A,Molon B

    更新日期:2020-11-06 00:00:00

  • miR-218-5p restores sensitivity to gemcitabine through PRKCE/MDR1 axis in gallbladder cancer.

    abstract::Gallbladder cancer (GBC) is one of the most common malignancy of the biliary tract characterized by its high chemoresistant tendency. Although great progresses have been made in recent decades for treating many cancers with anticancer drugs, effective therapeutics methods for anti-GBC are still lacking. Therefore, inv...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Wang H,Zhan M,Xu SW,Chen W,Long MM,Shi YH,Liu Q,Mohan M,Wang J

    更新日期:2017-05-11 00:00:00

  • CCAAT/enhancer binding protein beta protects muscle satellite cells from apoptosis after injury and in cancer cachexia.

    abstract::CCAAT/enhancer binding protein beta (C/EBPβ), a transcription factor expressed in muscle satellite cells (SCs), inhibits the myogenic program and is downregulated early in differentiation. In a conditional null model in which C/EBPβ expression is knocked down in paired box protein 7+ (Pax7+) SCs, cardiotoxin (CTX) inj...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Marchildon F,Fu D,Lala-Tabbert N,Wiper-Bergeron N

    更新日期:2016-02-25 00:00:00

  • Chloride channels are necessary for full platelet phosphatidylserine exposure and procoagulant activity.

    abstract::Platelets enhance thrombin generation at sites of vascular injury by exposing phosphatidylserine during necrosis-like cell death. Anoctamin 6 (Ano6) is required for Ca(2+)-dependent phosphatidylserine exposure and is defective in patients with Scott syndrome, a rare bleeding disorder. Ano6 may also form Cl(-) channels...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Harper MT,Poole AW

    更新日期:2013-12-19 00:00:00

  • Astrocytes are important mediators of Aβ-induced neurotoxicity and tau phosphorylation in primary culture.

    abstract::Alzheimer's disease (AD) is pathologically characterised by the age-dependent deposition of β-amyloid (Aβ) in senile plaques, intraneuronal accumulation of tau as neurofibrillary tangles, synaptic dysfunction and neuronal death. Neuroinflammation, typified by the accumulation of activated microglia and reactive astroc...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Garwood CJ,Pooler AM,Atherton J,Hanger DP,Noble W

    更新日期:2011-06-02 00:00:00

  • Is trehalose an autophagic inducer? Unraveling the roles of non-reducing disaccharides on autophagic flux and alpha-synuclein aggregation.

    abstract::Autophagy is a pivotal intracellular process by which cellular macromolecules are degraded upon various stimuli. A failure in the degradation of autophagic substrates such as impaired organelles and protein aggregates leads to their accumulations, which are characteristics of many neurodegenerative diseases. Pharmacol...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Yoon YS,Cho ED,Jung Ahn W,Won Lee K,Lee SJ,Lee HJ

    更新日期:2017-10-05 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

  • m6A methylation controls pluripotency of porcine induced pluripotent stem cells by targeting SOCS3/JAK2/STAT3 pathway in a YTHDF1/YTHDF2-orchestrated manner.

    abstract::Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) hold great promise for regenerative medicine, disease treatment, and organ transplantation. As the ethical issue of human ESCs and similarity of pig in human genome and physiological characteristics, the porcine iPSCs (piPSCs) have become an ideal ...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Wu R,Liu Y,Zhao Y,Bi Z,Yao Y,Liu Q,Wang F,Wang Y,Wang X

    更新日期:2019-02-20 00:00:00

  • Inhibition of p85, the non-catalytic subunit of phosphatidylinositol 3-kinase, exerts potent antitumor activity in human breast cancer cells.

    abstract::The phosphoinositide 3-kinases (PI3Ks) are heterodimers consisting of the catalytic subunit p110 and the regulatory subunit p85. The PI3K/Akt pathway is strongly deregulated in breast cancer (BC) representing one of the mechanisms of resistance to therapies. Therefore, the identification of inhibitors of PI3K componen...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Folgiero V,Di Carlo SE,Bon G,Spugnini EP,Di Benedetto A,Germoni S,Pia Gentileschi M,Accardo A,Milella M,Morelli G,Bossi G,Mottolese M,Falcioni R

    更新日期:2012-12-06 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

  • KLF5 inhibits STAT3 activity and tumor metastasis in prostate cancer by suppressing IGF1 transcription cooperatively with HDAC1.

    abstract::KLF5 is frequently deleted and downregulated in prostate cancer, and recently it has been reported that KLF5 loss is enriched in the aggressive branches of prostate cancer evolution. However, why KLF5 loss is associated with prostate cancer aggressiveness is still not clear. Herein, we analyzed KLF5 expression in TCGA...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Ma JB,Bai JY,Zhang HB,Jia J,Shi Q,Yang C,Wang X,He D,Guo P

    更新日期:2020-06-16 00:00:00

  • SOX12 promotes colorectal cancer cell proliferation and metastasis by regulating asparagine synthesis.

    abstract::The sex-determining region Y (SRY)-box (SOX) family has a crucial role in carcinogenesis and cancer progression. However, the role of SOX12 and the mechanism by which it is dysregulated in colorectal cancer (CRC) remain unclear. Here we analyzed SOX12 expression patterns in two independent CRC cohorts (cohort I, n = 3...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Du F,Chen J,Liu H,Cai Y,Cao T,Han W,Yi X,Qian M,Tian D,Nie Y,Wu K,Fan D,Xia L

    更新日期:2019-03-11 00:00:00

  • Increased expression of EHF via gene amplification contributes to the activation of HER family signaling and associates with poor survival in gastric cancer.

    abstract::The biological function of E26 transformation-specific (ETS) transcription factor EHF/ESE-3 in human cancers remains largely unknown, particularly gastric cancer. The aim of this study was to explore the role of EHF in tumorigenesis and its potential as a therapeutic target in gastric cancer. By using quantitative RT-...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Shi J,Qu Y,Li X,Sui F,Yao D,Yang Q,Shi B,Ji M,Hou P

    更新日期:2016-10-27 00:00:00

  • Excitotoxic cell death induces delayed proliferation of endogenous neuroprogenitor cells in organotypic slice cultures of the rat spinal cord.

    abstract::The aim of the present report was to investigate whether, in the mammalian spinal cord, cell death induced by transient excitotoxic stress could trigger activation and proliferation of endogenous neuroprogenitor cells as a potential source of a lesion repair process and the underlying time course. Because it is diffic...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Mazzone GL,Mladinic M,Nistri A

    更新日期:2013-10-31 00:00:00

  • Tumor suppressor WWOX binds to ΔNp63α and sensitizes cancer cells to chemotherapy.

    abstract::The WWOX tumor suppressor is a WW domain-containing protein. Its function in the cell has been shown to be mediated, in part, by interacting with its partners through its first WW (WW1) domain. Here, we demonstrated that WWOX via WW1 domain interacts with p53 homolog, ΔNp63α. This protein-protein interaction stabilize...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Salah Z,Bar-mag T,Kohn Y,Pichiorri F,Palumbo T,Melino G,Aqeilan RI

    更新日期:2013-01-31 00:00:00

  • Amlexanox, a selective inhibitor of IKBKE, generates anti-tumoral effects by disrupting the Hippo pathway in human glioblastoma cell lines.

    abstract::Glioblastoma multiforme (GBM) is the most prevalent form of malignant brain tumor. Amlexanox, a novel compound, has been shown to have anti-cancer potential. In this study, the anti-tumoral effects and the underlying mechanisms of amlexanox were investigated. Amlexanox significantly suppressed proliferation and invasi...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Liu Y,Lu J,Zhang Z,Zhu L,Dong S,Guo G,Li R,Nan Y,Yu K,Zhong Y,Huang Q

    更新日期:2017-08-31 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

  • 4-hydroxyphenylpyruvate dioxygenase promotes lung cancer growth via pentose phosphate pathway (PPP) flux mediated by LKB1-AMPK/HDAC10/G6PD axis.

    abstract::4-hydroxyphenylpyruvate dioxygenase (HPD) is an important modifier of tyrosine metabolism. However, the precise contribution of HPD to cancer metabolism and tumorigenesis remains unclear. In this study, we found that HPD was highly expressed in lung cancer and its higher expression correlated with poor prognosis in lu...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Shan C,Lu Z,Li Z,Sheng H,Fan J,Qi Q,Liu S,Zhang S

    更新日期:2019-07-08 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

  • Autophagy promotes MSC-mediated vascularization in cutaneous wound healing via regulation of VEGF secretion.

    abstract::Vascularization deficiency caused a lot of diseases, such as diabetes ulcer and myocardial infarction. Mesenchymal stem cells (MSCs), with the self-renewal and multipotent differentiation capacities, have been used for many diseases treatment through regulation microenvironment. Numerous studies reported that MSCs tra...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: An Y,Liu WJ,Xue P,Ma Y,Zhang LQ,Zhu B,Qi M,Li LY,Zhang YJ,Wang QT,Jin Y

    更新日期:2018-01-19 00:00:00

  • Inhibition of human mitochondrial peptide deformylase causes apoptosis in c-myc-overexpressing hematopoietic cancers.

    abstract::Inhibition of human mitochondrial peptide deformylase (HsPDF) depolarizes the mitochondrial membrane, reduces mitochondrial protein translation and causes apoptosis in Burkitt's lymphoma. We showed that HsPDF mRNA and protein levels were overexpressed in cancer cells and primary acute myeloid leukemia samples. Myc reg...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Sheth A,Escobar-Alvarez S,Gardner J,Ran L,Heaney ML,Scheinberg DA

    更新日期:2014-03-27 00:00:00

  • Correction to: RIP1 protects melanoma cells from apoptosis induced by BRAF/MEK inhibitors.

    abstract::Since publication of this paper, the authors have noticed that there were errors in Fig. 2A (the GAPDH of Mel-CV, Mel-CV.S, Mel-RMu and Mel-RMu.S), Fig. 2C (the GAPDH of Mel-CV.S and Mel-RMu.S), Fig. 3F (the GAPDH of Mel-CV.S and Mel-RMu.S), Fig. 3J(the GAPDH of Mel-RMu.S), Fig. 5C (the ERK1/2 of patient#3(post)), and...

    journal_title:Cell death & disease

    pub_type: 已发布勘误


    authors: Lei FX,Jin L,Liu XY,Lai F,Yan XG,Farrelly M,Guo ST,Zhao XH,Zhang XD

    更新日期:2019-03-05 00:00:00