miR-491-5p-induced apoptosis in ovarian carcinoma depends on the direct inhibition of both BCL-XL and EGFR leading to BIM activation.

Abstract:

:We sought to identify miRNAs that can efficiently induce apoptosis in ovarian cancer cells by overcoming BCL-X(L) and MCL1 anti-apoptotic activity, using combined computational and experimental approaches. We found that miR-491-5p efficiently induces apoptosis in IGROV1-R10 cells by directly inhibiting BCL-X(L) expression and by inducing BIM accumulation in its dephosphorylated form. This latter effect is due to direct targeting of epidermal growth factor receptor (EGFR) by miR-491-5p and consequent inhibition of downstream AKT and MAPK signalling pathways. Induction of apoptosis by miR-491-5p in this cell line is mimicked by a combination of EGFR inhibition together with a BH3-mimetic molecule. In contrast, SKOV3 cells treated with miR-491-5p maintain AKT and MAPK activity, do not induce BIM and do not undergo cell death despite BCL-XL and EGFR downregulation. In this cell line, sensitivity to miR-491-5p is restored by inhibition of both AKT and MAPK signalling pathways. Altogether, this work highlights the potential of miRNA functional studies to decipher cell signalling pathways or major regulatory hubs involved in cell survival to finally propose the rationale design of new strategies on the basis of pharmacological combinations.

journal_name

Cell Death Dis

journal_title

Cell death & disease

authors

Denoyelle C,Lambert B,Meryet-Figuière M,Vigneron N,Brotin E,Lecerf C,Abeilard E,Giffard F,Louis MH,Gauduchon P,Juin P,Poulain L

doi

10.1038/cddis.2014.389

subject

Has Abstract

pub_date

2014-10-09 00:00:00

pages

e1445

issn

2041-4889

pii

cddis2014389

journal_volume

5

pub_type

杂志文章
  • Pro-apoptotic miRNA-128-2 modulates ABCA1, ABCG1 and RXRα expression and cholesterol homeostasis.

    abstract::Aberrant regulation of cholesterol homeostasis is associated with obesity as well as multiple types of cancer. However, the mechanism behind these is largely missing. Here, we show that microRNA (miRNA)-128-2 is not only a pro-apoptotic microRNA but it also alters the expression of genes involved in cellular cholester...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2013.301

    authors: Adlakha YK,Khanna S,Singh R,Singh VP,Agrawal A,Saini N

    更新日期:2013-08-29 00:00:00

  • Preclinical screening of histone deacetylase inhibitors combined with ABT-737, rhTRAIL/MD5-1 or 5-azacytidine using syngeneic Vk*MYC multiple myeloma.

    abstract::Multiple myeloma (MM) is an incurable malignancy with an unmet need for innovative treatment options. Histone deacetylase inhibitors (HDACi) are a new class of anticancer agent that have demonstrated activity in hematological malignancies. Here, we investigated the efficacy and safety of HDACi (vorinostat, panobinosta...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2013.306

    authors: Matthews GM,Lefebure M,Doyle MA,Shortt J,Ellul J,Chesi M,Banks KM,Vidacs E,Faulkner D,Atadja P,Bergsagel PL,Johnstone RW

    更新日期:2013-09-12 00:00:00

  • Spermidine promotes stress resistance in Drosophila melanogaster through autophagy-dependent and -independent pathways.

    abstract::The naturally occurring polyamine spermidine (Spd) has recently been shown to promote longevity across species in an autophagy-dependent manner. Here, we demonstrate that Spd improves both survival and locomotor activity of the fruit fly Drosophila melanogaster upon exposure to the superoxide generator and neurotoxic ...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2012.139

    authors: Minois N,Carmona-Gutierrez D,Bauer MA,Rockenfeller P,Eisenberg T,Brandhorst S,Sigrist SJ,Kroemer G,Madeo F

    更新日期:2012-10-11 00:00:00

  • The HSP-RTK-Akt axis mediates acquired resistance to Ganetespib in HER2-positive breast cancer.

    abstract::Breast cancer is the leading cause of cancer-related death in women worldwide. Human epidermal growth factor receptor 2 (HER2)-positive subtype comprises 20% of sporadic breast cancers and is an aggressive disease. While targeted therapies have greatly improved its management, primary and acquired resistance remain a ...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-021-03414-3

    authors: Eyermann CE,Haley JD,Alexandrova EM

    更新日期:2021-01-26 00:00:00

  • Role of c-Abl and nephrin in podocyte cytoskeletal remodeling induced by angiotensin II.

    abstract::Our previous study showed that angiotensin II (Ang II) exposure diminished the interaction between nephrin and c-Abl, then c-Abl mediated SHIP2-Akt pathway in the process of podocyte injury in vivo and vitro. However, the relationship between nephrin and c-Abl was unknown. Recently, various studies showed that nephrin...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-017-0225-y

    authors: Ma Y,Yang Q,Zhong Z,Liang W,Zhang L,Yang Y,Ding G

    更新日期:2018-02-07 00:00:00

  • The chemokine receptor CCR10 promotes inflammation-driven hepatocarcinogenesis via PI3K/Akt pathway activation.

    abstract::G-protein-coupled receptor (GPCR)-related proteins are dysregulated and the GPCR CC-chemokine receptor 10 (CCR10) is significantly upregulated in inflammation-driven HCC. However, CCR10's role in inflammation-driven hepatocarcinogenesis remains unknown. The aim of this study was to evaluate the role of CCR10 in inflam...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-018-0267-9

    authors: Wu Q,Chen JX,Chen Y,Cai LL,Wang XZ,Guo WH,Zheng JF

    更新日期:2018-02-14 00:00:00

  • Ex vivo culture of intestinal crypt organoids as a model system for assessing cell death induction in intestinal epithelial cells and enteropathy.

    abstract::Intestinal epithelial cells (IECs) not only have a critical function in the absorption of nutrients, but also act as a physical barrier between our body and the outside world. Damage and death of the epithelial cells lead to the breakdown of this barrier function and inflammation due to access of the immune system to ...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2014.183

    authors: Grabinger T,Luks L,Kostadinova F,Zimberlin C,Medema JP,Leist M,Brunner T

    更新日期:2014-05-15 00:00:00

  • miR-425 deficiency promotes necroptosis and dopaminergic neurodegeneration in Parkinson's disease.

    abstract::A major hallmark of Parkinson's disease (PD) is the degeneration of dopaminergic neurons in the substantia nigra, and the causative mechanism is thought to be the activation of programmed neuronal death. Necroptosis is a regulated process of cell death triggered by RIPK1. Although the pathophysiology of PD has been st...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-019-1809-5

    authors: Hu YB,Zhang YF,Wang H,Ren RJ,Cui HL,Huang WY,Cheng Q,Chen HZ,Wang G

    更新日期:2019-08-05 00:00:00

  • Long noncoding RNA SNHG14 facilitates colorectal cancer metastasis through targeting EZH2-regulated EPHA7.

    abstract::Accumulating evidence suggested the participation of long noncoding RNAs (lncRNAs) in regulating various biological processes so as to affecting cancer progression. However, the functional role of most lncRNAs in colorectal carcer (CRC) is still largely covered. In the present study, we disclosed SNHG14 as a carcinoge...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-019-1707-x

    authors: Di W,Weinan X,Xin L,Zhiwei Y,Xinyue G,Jinxue T,Mingqi L

    更新日期:2019-07-04 00:00:00

  • Tryptophan-kynurenine pathway attenuates β-catenin-dependent pro-parasitic role of STING-TICAM2-IRF3-IDO1 signalosome in Toxoplasma gondii infection.

    abstract::Recent studies have documented the diverse role of host immunity in infection by the protozoan parasite, Toxoplasma gondii. However, the contribution of the β-catenin pathway in this process has not been explored. Here, we show that AKT-mediated phosphorylated β-catenin supports T. gondii multiplication which is arres...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-019-1420-9

    authors: Majumdar T,Sharma S,Kumar M,Hussain MA,Chauhan N,Kalia I,Sahu AK,Rana VS,Bharti R,Haldar AK,Singh AP,Mazumder S

    更新日期:2019-02-15 00:00:00

  • Human embryonic stem cell neural differentiation and enhanced cell survival promoted by hypoxic preconditioning.

    abstract::Transplantation of neural progenitors derived from human embryonic stem cells (hESCs) provides a potential therapy for ischemic stroke. However, poor graft survival within the host environment has hampered the benefits and applications of cell-based therapies. The present investigation tested a preconditioning strateg...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2009.22

    authors: Francis KR,Wei L

    更新日期:2010-01-01 00:00:00

  • Long non-coding RNA LRRC75A-AS1 facilitates triple negative breast cancer cell proliferation and invasion via functioning as a ceRNA to modulate BAALC.

    abstract::As a common female malignancy, triple-negative breast cancer (TNBC) is the most serious subtype in breast cancer (BC). BAALC binder of MAP3K1 and KLF4 (BAALC) is a common oncogene in acute myelocytic leukemia (AML). We sought to explore the role of BAALC in TNBC. In this study, BAALC was significantly upregulated in T...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-020-02821-2

    authors: Li S,Wu D,Jia H,Zhang Z

    更新日期:2020-08-18 00:00:00

  • Microglia-derived TNF-α mediates endothelial necroptosis aggravating blood brain-barrier disruption after ischemic stroke.

    abstract::Endothelium (EC) is a key component of blood-brain barrier (BBB), and has an important position in the neurovascular unit. Its dysfunction and death after cerebral ischemic/reperfusion (I/R) injury not only promote evolution of neuroinflammation and brain edema, but also increase the risk of intracerebral hemorrhage o...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-019-1716-9

    authors: Chen AQ,Fang Z,Chen XL,Yang S,Zhou YF,Mao L,Xia YP,Jin HJ,Li YN,You MF,Wang XX,Lei H,He QW,Hu B

    更新日期:2019-06-20 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

  • miR-6086 inhibits ovarian cancer angiogenesis by downregulating the OC2/VEGFA/EGFL6 axis.

    abstract::miRNAs have emerged as a pivotal component of gene regulatory networks, mediating cytokines secretion, cell cycle, and differentiation regulation. However, how miRNAs collaborate with transcription factors and downstream effector proteins that determine the fate of ovarian cancer cells remains to be understood, especi...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-020-2501-5

    authors: Wu B,Zhang L,Yu Y,Lu T,Zhang Y,Zhu W,Song Q,Lv C,Guo J,Tian Y,Deng N

    更新日期:2020-05-11 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

    doi:10.1038/s41419-020-03151-z

    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

  • MicroRNA-587 antagonizes 5-FU-induced apoptosis and confers drug resistance by regulating PPP2R1B expression in colorectal cancer.

    abstract::Drug resistance is one of the major hurdles for cancer treatment. However, the underlying mechanisms are still largely unknown and therapeutic options remain limited. In this study, we show that microRNA (miR)-587 confers resistance to 5-fluorouracil (5-FU)-induced apoptosis in vitro and reduces the potency of 5-FU in...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2015.200

    authors: Zhang Y,Talmon G,Wang J

    更新日期:2015-08-06 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

    doi:10.1038/cddis.2014.337

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

    更新日期:2014-08-14 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

  • The epigenetically regulated miR-494 associates with stem-cell phenotype and induces sorafenib resistance in hepatocellular carcinoma.

    abstract::Hepatocellular carcinoma (HCC) represents the second cause of cancer-related mortality worldwide and is associated with poor prognosis, especially in patients not amenable for curative treatments. The multi-kinase inhibitor sorafenib represents the first-line treatment option for advanced HCC; nevertheless, its effect...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-017-0076-6

    authors: Pollutri D,Patrizi C,Marinelli S,Giovannini C,Trombetta E,Giannone FA,Baldassarre M,Quarta S,Vandewynckel YP,Vandierendonck A,Van Vlierberghe H,Porretti L,Negrini M,Bolondi L,Gramantieri L,Fornari F

    更新日期:2018-01-05 00:00:00

  • Resveratrol regulates mitochondrial reactive oxygen species homeostasis through Sirt3 signaling pathway in human vascular endothelial cells.

    abstract::Mitochondrial reactive oxygen species (mtROS) homeostasis plays an essential role in preventing oxidative injury in endothelial cells, an initial step in atherogenesis. Resveratrol (RSV) possesses a variety of cardioprotective activities, however, little is known regarding the effects of RSV on mtROS homeostasis in en...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2014.530

    authors: Zhou X,Chen M,Zeng X,Yang J,Deng H,Yi L,Mi MT

    更新日期:2014-12-18 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

    doi:10.1038/s41419-019-1865-x

    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

  • 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

    doi:10.1038/s41419-017-0082-8

    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

  • Ferroportin downregulation promotes cell proliferation by modulating the Nrf2-miR-17-5p axis in multiple myeloma.

    abstract::Recent findings demonstrate that aberrant downregulation of the iron-exporter protein, ferroportin (FPN1), is associated with poor prognosis and osteoclast differentiation in multiple myeloma (MM). Here, we show that FPN1 was downregulated in MM and that clustered regularly interspaced short palindromic repeat (CRISPR...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-019-1854-0

    authors: Kong Y,Hu L,Lu K,Wang Y,Xie Y,Gao L,Yang G,Xie B,He W,Chen G,Wu H,Wu X,Zhan F,Shi J

    更新日期:2019-08-19 00:00:00

  • HMGB1 promotes ERK-mediated mitochondrial Drp1 phosphorylation for chemoresistance through RAGE in colorectal cancer.

    abstract::Dysfunctional mitochondria have been shown to enhance cancer cell proliferation, reduce apoptosis, and increase chemoresistance. Chemoresistance develops in nearly all patients with colorectal cancer, leading to a decrease in the therapeutic efficacies of anticancer agents. However, the effect of dynamin-related prote...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-018-1019-6

    authors: Huang CY,Chiang SF,Chen WT,Ke TW,Chen TW,You YS,Lin CY,Chao KSC,Huang CY

    更新日期:2018-09-26 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

    doi:10.1038/cddis.2013.6

    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

  • circRNA-002178 act as a ceRNA to promote PDL1/PD1 expression in lung adenocarcinoma.

    abstract::Circular RNAs (circRNAs) have been identified play a vital role in various different types of cancer via sponging miRNAs (microRNAs). However, their role in lung adenocarcinoma (LUAD) remains largely unclear. In this study, we systematically characterized the circRNA expression profiles in the LUAD cancer tissues and ...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-020-2230-9

    authors: Wang J,Zhao X,Wang Y,Ren F,Sun D,Yan Y,Kong X,Bu J,Liu M,Xu S

    更新日期:2020-01-16 00:00:00

  • Absence of cyclin-dependent kinase inhibitor p27 or p18 increases efficiency of iPSC generation without induction of iPSC genomic instability.

    abstract::Mechanisms underlying the generation of induced pluripotent stem cells (iPSC) and keeping iPSC stability remain to be further defined. Accumulated evidences showed that iPSC reprogramming may be controlled by the cell-division-rate-dependent model. Here we reported effects of absence of mouse p27 or p18 on iPSC genera...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-019-1502-8

    authors: Zhan Z,Song L,Zhang W,Gu H,Cheng H,Zhang Y,Yang Y,Ji G,Feng H,Cheng T,Li Y

    更新日期:2019-03-20 00:00:00

  • Retraction Note: HDAC6 inhibitor TST strengthens the antiproliferative effects of PI3K/mTOR inhibitor BEZ235 in breast cancer cells via suppressing RTK activation.

    abstract::An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...

    journal_title:Cell death & disease

    pub_type: 杂志文章,撤回出版物

    doi:10.1038/s41419-019-1866-9

    authors: Sun S,Zhang Y,Zheng J,Duan B,Cui J,Chen Y,Deng W,Ye B,Liu L,Chen Y,Du J,Gu L

    更新日期:2019-08-22 00:00:00

  • LINC81507 act as a competing endogenous RNA of miR-199b-5p to facilitate NSCLC proliferation and metastasis via regulating the CAV1/STAT3 pathway.

    abstract::Lung cancer is the leading cause of cancer-related mortality worldwide. Recently, accumulating data indicate that long noncoding RNAs (LncRNAs) function as novel crucial regulators of diverse biological processes, including proliferation and metastasis, in tumorigenesis. Lnc NONHSAT081507.1 (LINC81507) is associated w...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-019-1740-9

    authors: Peng W,He D,Shan B,Wang J,Shi W,Zhao W,Peng Z,Luo Q,Duan M,Li B,Cheng Y,Dong Y,Tang F,Zhang C,Duan C

    更新日期:2019-07-11 00:00:00