E2F1 mediated DDX11 transcriptional activation promotes hepatocellular carcinoma progression through PI3K/AKT/mTOR pathway.

Abstract:

:The DEAD/DEAH box helicase 11 (DDX11) plays vital roles in regulating the initiation of DNA replication. However, its precise function and regulation in hepatocellular carcinoma (HCC) have never been reported yet. In the current study, we found that DDX11 was overexpressed in HCC tissues. High DDX11 expression was positively correlated with large tumor size, tumor multiplicity, late tumor-node-metastasis (TNM) stage and poor prognosis. Additional, gain-of-function and loss-of-function experimental results revealed that DDX11 overexpression promoted HCC cell proliferation, migration, invasion and inhibited cell apoptosis in vitro. Overexpression of DDX11 also enhanced HCC tumorigenicity in vivo. Furthermore, DDX11 was transcriptionally regulated by transcription factor E2F1 in HCC, as demonstrated by chromatin immunoprecipitation (Ch-IP) and luciferase reporter assays. Mechanistically, E2F1/DDX11 axis promoted HCC cell proliferation, migration and invasion, at least in part, through activating PI3K/AKT/mTOR signaling pathway. Conclusively, our study demonstrates that E2F1-enhanced DDX11 expression promotes HCC progression through PI3K/AKT/mTOR pathway and DDX11 might be a potential therapeutic and prognostic target for HCC treatment.

journal_name

Cell Death Dis

journal_title

Cell death & disease

authors

Yu Y,Zhao D,Li K,Cai Y,Xu P,Li R,Li J,Chen X,Chen P,Cui G

doi

10.1038/s41419-020-2478-0

subject

Has Abstract

pub_date

2020-04-24 00:00:00

pages

273

issue

4

issn

2041-4889

pii

10.1038/s41419-020-2478-0

journal_volume

11

pub_type

杂志文章
  • 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

    doi:10.1038/cddis.2017.396

    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

  • Ionizing radiations sustain glioblastoma cell dedifferentiation to a stem-like phenotype through survivin: possible involvement in radioresistance.

    abstract::Glioblastomas (GBM) are some bad prognosis brain tumors despite a conventional treatment associating surgical resection and subsequent radio-chemotherapy. Among these heterogeneous tumors, a subpopulation of chemo- and radioresistant GBM stem-like cells appears to be involved in the systematic GBM recurrence. Moreover...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2014.509

    authors: Dahan P,Martinez Gala J,Delmas C,Monferran S,Malric L,Zentkowski D,Lubrano V,Toulas C,Cohen-Jonathan Moyal E,Lemarie A

    更新日期:2014-11-27 00:00:00

  • Inhibition of autophagy increased AGE/ROS-mediated apoptosis in mesangial cells.

    abstract::The aim of our study was to investigate the role of autophagy, a homeostatic process involved in the lysosomal degradation of damaged cell organelles and proteins, in regulating the survival of mesangial cells treated with advanced glycation end products (AGEs). In the present study, AGEs induced mitochondrial depolar...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2016.322

    authors: Xu L,Fan Q,Wang X,Zhao X,Wang L

    更新日期:2016-11-03 00:00:00

  • Downregulation of FAP suppresses cell proliferation and metastasis through PTEN/PI3K/AKT and Ras-ERK signaling in oral squamous cell carcinoma.

    abstract::It is largely recognized that fibroblast activation protein (FAP) is expressed in cancer-associated fibroblasts (CAFs) of many human carcinomas. Furthermore, FAP was recently also reported to be expressed in carcinoma cells of the breast, stomach, pancreatic ductal adenocarcinoma, colorectum, and uterine cervix. The c...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2014.122

    authors: Wang H,Wu Q,Liu Z,Luo X,Fan Y,Liu Y,Zhang Y,Hua S,Fu Q,Zhao M,Chen Y,Fang W,Lv X

    更新日期:2014-04-10 00:00:00

  • MicroRNA-195 prevents dendritic degeneration and neuron death in rats following chronic brain hypoperfusion.

    abstract::Impaired synaptic plasticity and neuron loss are hallmarks of Alzheimer's disease and vascular dementia. Here, we found that chronic brain hypoperfusion (CBH) by bilateral common carotid artery occlusion (2VO) decreased the total length, numbers and crossings of dendrites and caused neuron death in rat hippocampi and ...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2017.243

    authors: Chen X,Jiang XM,Zhao LJ,Sun LL,Yan ML,Tian Y,Zhang S,Duan MJ,Zhao HM,Li WR,Hao YY,Wang LB,Xiong QJ,Ai J

    更新日期:2017-06-01 00:00:00

  • Survivin, a novel target of the Hedgehog/GLI signaling pathway in human tumor cells.

    abstract::Survivin, an important antiapoptotic protein, is expressed in tumors, whereas in normal tissues the expression of this protein is extremely low, defining a role for survivin as a cancer gene. Survivin exhibits multifunctional activity in tumor cells. However, why survivin expression is sharply and invariably restricte...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2015.389

    authors: Vlčková K,Ondrušová L,Vachtenheim J,Réda J,Dundr P,Zadinová M,Žáková P,Poučková P

    更新日期:2016-01-14 00:00:00

  • PTPL1 and PKCδ contribute to proapoptotic signalling in prostate cancer cells.

    abstract::PTPL1 is a non-receptor protein tyrosine phosphatase involved in apoptosis regulation, although controversial findings have been reported in different cancer types. We report here a proapoptotic role for PTPL1 in PC3 and LNCaP prostate cancer cells, as its absence induces apoptosis resistance upon treatment with diffe...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2013.90

    authors: Castilla C,Chinchón D,Medina R,Torrubia FJ,Japón MA,Sáez C

    更新日期:2013-04-04 00:00:00

  • The p75 receptor mediates axon growth inhibition through an association with PIR-B.

    abstract::The Nogo receptor and paired immunoglobulin-like receptor B (PIR-B) are receptors for three myelin-derived axon-growth inhibitors, including myelin-associated glycoprotein (MAG). In this study, we report that the p75 receptor is required for the signal transduction of PIR-B, which interacted with p75 upon ligand bindi...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2011.85

    authors: Fujita Y,Takashima R,Endo S,Takai T,Yamashita T

    更新日期:2011-09-01 00:00:00

  • Primary cilia mediate mitochondrial stress responses to promote dopamine neuron survival in a Parkinson's disease model.

    abstract::A primary cilium is an antenna-like structure on the cell surface that plays a crucial role in sensory perception and signal transduction. Mitochondria, the 'powerhouse' of the cell, control cell survival, and death. The cellular ability to remove dysfunctional mitochondria through mitophagy is important for cell surv...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-019-2184-y

    authors: Bae JE,Kang GM,Min SH,Jo DS,Jung YK,Kim K,Kim MS,Cho DH

    更新日期:2019-12-16 00:00:00

  • Flavones hydroxylated at 5, 7, 3' and 4' ameliorate skin fibrosis via inhibiting activin receptor-like kinase 5 kinase activity.

    abstract::Skin fibrosis is mainly characterized by excessive collagen deposition. Studies have recently identified a number of flavonoids with variable structures that have the potency of inhibiting collagen synthesis and thus attenuating organ fibrosis. In this study, we found that flavones with 5, 7, 3', 4' hydroxy substituti...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-019-1333-7

    authors: Zhang Y,Wang J,Zhou S,Xie Z,Wang C,Gao Y,Zhou J,Zhang X,Li Q

    更新日期:2019-02-11 00:00:00

  • Neutrophil extracellular traps promote macrophage pyroptosis in sepsis.

    abstract::In response to infection, polymorphonuclear neutrophils (PMN) are recruited in the infectious sites, and employ three major strategies to fight against the microbes including phagocytosis, degranulation, and neutrophil extracellular traps (NETs). NETs are a meshwork of chromatin fibers mixed with granule-derived antim...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-018-0538-5

    authors: Chen L,Zhao Y,Lai D,Zhang P,Yang Y,Li Y,Fei K,Jiang G,Fan J

    更新日期:2018-05-22 00:00:00

  • Mitochondrial ferritin protects the murine myocardium from acute exhaustive exercise injury.

    abstract::Mitochondrial ferritin (FtMt) is a mitochondrially localized protein possessing ferroxidase activity and the ability to store iron. FtMt overexpression in cultured cells protects against oxidative damage by sequestering redox-active, intracellular iron. Here, we found that acute exhaustive exercise significantly incre...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2016.372

    authors: Wu W,Chang S,Wu Q,Xu Z,Wang P,Li Y,Yu P,Gao G,Shi Z,Duan X,Chang YZ

    更新日期:2016-11-17 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

    doi:10.1038/cddis.2010.54

    authors: Janson V,Johansson A,Grankvist K

    更新日期:2010-09-23 00:00:00

  • Bone-targeted lncRNA OGRU alleviates unloading-induced bone loss via miR-320-3p/Hoxa10 axis.

    abstract::Unloading-induced bone loss is a threat to human health and can eventually result in osteoporotic fractures. Although the underlying molecular mechanism of unloading-induced bone loss has been broadly elucidated, the pathophysiological role of long noncoding RNAs (lncRNAs) in this process is unknown. Here, we identifi...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-020-2574-1

    authors: Wang K,Wang Y,Hu Z,Zhang L,Li G,Dang L,Tan Y,Cao X,Shi F,Zhang S,Zhang G

    更新日期:2020-05-19 00:00:00

  • Loss of ATF3 exacerbates liver damage through the activation of mTOR/p70S6K/ HIF-1α signaling pathway in liver inflammatory injury.

    abstract::Activating transcription factor 3 (ATF3) is a stress-induced transcription factor that plays important roles in regulating immune and metabolic homeostasis. Activation of the mechanistic target of rapamycin (mTOR) and hypoxia-inducible factor (HIF) transcription factors are crucial for the regulation of immune cell fu...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-018-0894-1

    authors: Zhu Q,Wang H,Jiang B,Ni X,Jiang L,Li C,Wang X,Zhang F,Ke B,Lu L

    更新日期:2018-09-05 00:00:00

  • The role of autophagy in asparaginase-induced immune suppression of macrophages.

    abstract::Erwinia asparaginase, a bacteria-derived enzyme drug, has been used in the treatment of various cancers, especially acute lymphoblastic leukemia (ALL). One of the most significant side effects associated with asparaginase administration is immune suppression, which limits its application in clinic. Macrophages are pha...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2017.144

    authors: Song P,Wang Z,Zhang X,Fan J,Li Y,Chen Q,Wang S,Liu P,Luan J,Ye L,Ju D

    更新日期:2017-03-30 00:00:00

  • Clinical-grade human umbilical cord-derived mesenchymal stem cells reverse cognitive aging via improving synaptic plasticity and endogenous neurogenesis.

    abstract::Cognitive aging is a leading public health concern with the increasing aging population, but there is still lack of specific interventions directed against it. Recent studies have shown that cognitive function is intimately affected by systemic milieu in aging brain, and improvement of systemic environment in aging br...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2017.316

    authors: Cao N,Liao T,Liu J,Fan Z,Zeng Q,Zhou J,Pei H,Xi J,He L,Chen L,Nan X,Jia Y,Yue W,Pei X

    更新日期:2017-08-10 00:00:00

  • PI3K/mTOR pathway inhibitors sensitize chronic myeloid leukemia stem cells to nilotinib and restore the response of progenitors to nilotinib in the presence of stem cell factor.

    abstract::Nilotinib is a second-generation tyrosine kinase inhibitor, designed to specifically inhibit break-point cluster region (BCR)-Abelson (ABL) and developed to treat chronic myeloid leukemia (CML) in patients showing a resistance to imatinib. We previously demonstrated that nilotinib-induced apoptosis was reduced by stem...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2013.309

    authors: Airiau K,Mahon FX,Josselin M,Jeanneteau M,Belloc F

    更新日期:2013-10-03 00:00:00

  • Eicosapentaenoic acid attenuates dexamethasome-induced apoptosis by inducing adaptive autophagy via GPR120 in murine bone marrow-derived mesenchymal stem cells.

    abstract::Long-term use of glucocorticoids is a widespread clinical problem, which currently has no effective solution other than discontinuing the use. Eicosapentaenoic acid (EPA), an omega-3 long chain polyunsaturated fatty acid (n-3 PUFA), which is largely contained in fish or fish oil, has been reported to promote cell viab...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2016.144

    authors: Gao B,Han YH,Wang L,Lin YJ,Sun Z,Lu WG,Hu YQ,Li JQ,Lin XS,Liu BH,Jie Q,Yang L,Luo ZJ

    更新日期:2016-05-26 00:00:00

  • WDR79 promotes the proliferation of non-small cell lung cancer cells via USP7-mediated regulation of the Mdm2-p53 pathway.

    abstract::WD repeat protein 79 (WDR79) is a member of the WD-repeat protein family and functions as a scaffold protein during telomerase assembly, Cajal body formation and DNA double strand break repair. We have previously shown that WDR79 is frequently overexpressed in cell lines and tissues derived from non-small cell lung ca...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2017.162

    authors: Sun Y,Cao L,Sheng X,Chen J,Zhou Y,Yang C,Deng T,Ma H,Feng P,Liu J,Tan W,Ye M

    更新日期:2017-04-13 00:00:00

  • Nicotinamide N-methyltransferase expression in SH-SY5Y neuroblastoma and N27 mesencephalic neurones induces changes in cell morphology via ephrin-B2 and Akt signalling.

    abstract::Nicotinamide N-methyltransferase (NNMT, E.C. 2.1.1.1) N-methylates nicotinamide to produce 1-methylnicotinamide (MeN). We have previously shown that NNMT expression protected against neurotoxin-mediated cell death by increasing Complex I (CxI) activity, resulting in increased ATP synthesis. This was mediated via prote...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2013.200

    authors: Thomas MG,Saldanha M,Mistry RJ,Dexter DT,Ramsden DB,Parsons RB

    更新日期:2013-06-13 00:00:00

  • Altering cell death pathways as an approach to cure HIV infection.

    abstract::Recent cases of successful control of human immunodeficiency virus (HIV) by bone marrow transplant in combination with suppressive antiretroviral therapy (ART) and very early initiation of ART have provided proof of concept that HIV infection might now be cured. Current efforts focusing on gene therapy, boosting HIV-s...

    journal_title:Cell death & disease

    pub_type: 杂志文章,评审

    doi:10.1038/cddis.2013.248

    authors: Badley AD,Sainski A,Wightman F,Lewin SR

    更新日期:2013-07-11 00:00:00

  • High-fat diet feeding and palmitic acid increase CRC growth in β2AR-dependent manner.

    abstract::Epidemiology studies indicate that consumption of high-fat diet (HFD) is directly associated with the development of colorectal cancer (CRC). However, the exact component in HFD and the mechanism underlying its effect on CRC growth remained unclear. Our study shows that HFD feeding increases β2AR expression in the xen...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-019-1958-6

    authors: Fatima S,Hu X,Huang C,Zhang W,Cai J,Huang M,Gong RH,Chen M,Ho AHM,Su T,Wong HLX,Bian Z,Kwan HY

    更新日期:2019-09-26 00:00:00

  • Reduction of the ATPase inhibitory factor 1 (IF1) leads to visual impairment in vertebrates.

    abstract::In vertebrates, mitochondria are tightly preserved energy producing organelles, which sustain nervous system development and function. The understanding of proteins that regulate their homoeostasis in complex animals is therefore critical and doing so via means of systemic analysis pivotal to inform pathophysiological...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-018-0578-x

    authors: Martín-Jiménez R,Faccenda D,Allen E,Reichel HB,Arcos L,Ferraina C,Strobbe D,Russell C,Campanella M

    更新日期:2018-06-04 00:00:00

  • Imbalance of the spindle-assembly checkpoint promotes spindle poison-mediated cytotoxicity with distinct kinetics.

    abstract::Disrupting microtubule dynamics with spindle poisons activates the spindle-assembly checkpoint (SAC) and induces mitotic cell death. However, mitotic exit can occur prematurely without proper chromosomal segregation or cytokinesis by a process termed mitotic slippage. It remains controversial whether mitotic slippage ...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-019-1539-8

    authors: Zeng X,Xu WK,Lok TM,Ma HT,Poon RYC

    更新日期:2019-04-05 00:00:00

  • p53 cooperates with SIRT6 to regulate cardiolipin de novo biosynthesis.

    abstract::The tumor suppressor p53 has critical roles in regulating lipid metabolism, but whether and how p53 regulates cardiolipin (CL) de novo biosynthesis is unknown. Here, we report that p53 physically interacts with histone deacetylase SIRT6 in vitro and in vivo, and this interaction increases following palmitic acid (PA) ...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-018-0984-0

    authors: Li M,Hou T,Gao T,Lu X,Yang Q,Zhu Q,Li Z,Liu C,Mu G,Liu G,Bao Y,Wen H,Wang L,Wang H,Zhao Y,Gu W,Yang Y,Zhu WG

    更新日期:2018-09-20 00:00:00

  • LncRNA SNORD3A specifically sensitizes breast cancer cells to 5-FU by sponging miR-185-5p to enhance UMPS expression.

    abstract::Breast cancer is the most common cancer type in women. Long non-coding RNAs (lncRNAs) have been reported as potential new diagnostic markers, prognostic factors, and therapeutic targets in cancer. However, the specific roles and mechanisms of lncRNAs in breast cancer remain to be elucidated. Here we demonstrated the d...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-020-2557-2

    authors: Luo L,Zhang J,Tang H,Zhai D,Huang D,Ling L,Wang X,Liu T,Zhang Q,Zhang Z,He Z,Zheng G

    更新日期:2020-05-07 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

    doi:10.1038/s41419-019-1373-z

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

    更新日期:2019-03-07 00:00:00

  • Early downregulation of Mcl-1 regulates apoptosis triggered by cardiac glycoside UNBS1450.

    abstract::Cardiac glycosides (CGs), prescribed to treat cardiovascular alterations, display potent anti-cancer activities. Despite their well-established target, the sodium/potassium (Na(+)/K(+))-ATPase, downstream mechanisms remain poorly elucidated. UNBS1450 is a hemi-synthetic cardenolide derived from 2″-oxovorusharin extrac...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2015.134

    authors: Cerella C,Muller F,Gaigneaux A,Radogna F,Viry E,Chateauvieux S,Dicato M,Diederich M

    更新日期:2015-06-11 00:00:00

  • M2 macrophages promote NSCLC metastasis by upregulating CRYAB.

    abstract::The mechanism by which tumor-associated macrophages (TAMs) affect cancer progression is not fully understood. This study developed a microfluidic-based co-culture device to mimic the tumor microenvironment to assess TAM effects on invasion and metastasis in NSCLC. The results showed lung carcinoma cells could cause ma...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-019-1618-x

    authors: Guo Z,Song J,Hao J,Zhao H,Du X,Li E,Kuang Y,Yang F,Wang W,Deng J,Wang Q

    更新日期:2019-05-16 00:00:00