Abstract:
:The development of prostate cancer (PCa) from androgen-deprivation therapy (ADT) sensitive to castration resistant (CRPC) seriously impacts life quality and survival of PCa patients. Emerging evidence shows that long noncoding RNAs (lncRNAs) play vital roles in cancer initiation and progression. However, the inherited mechanisms of how lncRNAs participate in PCa progression and treatment resistance remain unclear. Here, we found that a long noncoding RNA LINC00675 was upregulated in androgen-insensitive PCa cell lines and CRPC patients, which promoted PCa progression both in vitro and in vivo. Knockdown of LINC00675 markedly suppressed tumor formation and attenuated enzalutamide resistance of PCa cells. Mechanistically, LINC00675 could directly modulate androgen receptor's (AR) interaction with mouse double minute-2 (MDM2) and block AR's ubiquitination by binding to it. Meanwhile, LINC00675 could bind to GATA2 mRNA and stabilize its expression level, in which GATA2 could act as a co-activator in the AR signaling pathway. Notably, we treated subcutaneous xenografts models with enzalutamide and antisense oligonucleotides (ASO) targeting LINC00675 in vivo and found that targeting LINC00675 would benefit androgen-deprivation-insensitive models. Our findings disclose that the LINC00675/MDM2/GATA2/AR signaling axis is a potential therapeutic target for CRPC patients.
journal_name
Cell Death Disjournal_title
Cell death & diseaseauthors
Yao M,Shi X,Li Y,Xiao Y,Butler W,Huang Y,Du L,Wu T,Bian X,Shi G,Ye D,Fu G,Wang J,Ren Sdoi
10.1038/s41419-020-02856-5subject
Has Abstractpub_date
2020-08-15 00:00:00pages
638issue
8issn
2041-4889pii
10.1038/s41419-020-02856-5journal_volume
11pub_type
杂志文章abstract::Murine double minute-2 (MDM2) is an E3-ubiquitin ligase and the main negative regulator of tumor suppressor gene p53. MDM2 has also a non-redundant function as a modulator of NF-kB signaling. As such it promotes proliferation and inflammation. MDM2 is highly expressed in the unchallenged tubular epithelial cells and w...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2016.390
更新日期:2016-11-24 00:00:00
abstract::Non-small cell lung cancer (NSCLC) has the highest incidence of cancer-related death worldwide and a high medical need for more effective therapies. Small-molecule inhibitors of the bromodomain and extra terminal domain (BET) family such as JQ1, I-BET762 and OTX-015 are active in a wide range of different cancer types...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2016.271
更新日期:2016-09-08 00:00:00
abstract::Triple-negative breast cancers (TNBCs) are aggressive forms of breast carcinoma associated with a high rate of recidivism. In this paper, we report the production of mammospheres from three lines of TNBC cells and demonstrate that both parthenolide (PN) and its soluble analog dimethylaminoparthenolide (DMAPT) suppress...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2016.94
更新日期:2016-04-14 00:00:00
abstract::Primary cells respond to irradiation by activation of the DNA damage response and cell cycle arrest, which eventually leads to senescence or apoptosis. It is not clear in detail which signaling pathways or networks regulate the induction of either apoptosis or senescence. Primary human fibroblasts are able to withstan...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2013.15
更新日期:2013-02-14 00:00:00
abstract::Glioblastoma multiform (GBM) is the most common brain tumor characterized by a dismal prognosis. GBM cancer stem cells (gCSC) or tumor-initiating cells are the cell population within the tumor-driving therapy resistance and recurrence. While temozolomide (TMZ), an alkylating agent, constitutes the first-line chemother...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1477-5
更新日期:2019-03-13 00:00:00
abstract::Parkinson's disease (PD), the second most common neurodegenerative disorder, is characterized by dopaminergic neuronal loss that initiates in the substantia nigra pars compacta and by the formation of intracellular inclusions mainly constituted by aberrant α-synuclein (α-syn) deposits known as Lewy bodies. Most cases ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-2092-1
更新日期:2019-11-12 00:00:00
abstract::Enhanced Myd88 expression has been found in various parenchymal tumors especially in hepatocellular carcinoma with little mechanism of its upregulation known. A lot of long non-coding RNAs are reported to regulate the protein-coding genes which have location association through various mechanisms. In our study we conf...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2017.519
更新日期:2017-10-12 00:00:00
abstract::Granzyme B (GZMB) is a proapoptotic serine protease that is released by cytotoxic lymphocytes. However, GZMB can also be produced by other cell types and is capable of cleaving extracellular matrix (ECM) proteins. GZMB contributes to abdominal aortic aneurysm (AAA) through an extracellular, perforin-independent mechan...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2011.88
更新日期:2011-09-08 00:00:00
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
更新日期:2015-08-06 00:00:00
abstract::Melanoma is a kind of tumor that originates from melanocytes and is characterized by chemoresistance and distant metastasis. Although the complete pathogenesis of melanoma remains unclear, increasing evidence suggests that circular RNAs (circRNAs) may be involved. In the present study, we identified a circular RNA, ci...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-2444-x
更新日期:2020-04-23 00:00:00
abstract::N-myc and STAT interactor (NMI) has been proved to bind to different transcription factors to regulate a variety of signaling mechanisms including DNA damage, cell cycle and epithelial-mesenchymal transition. However, the role of NMI in the regulation of cancer stem cells (CSCs) remains poorly understood. In this stud...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2017.200
更新日期:2017-05-11 00:00:00
abstract::Traumatic brain injury (TBI) activates multiple neuronal cell death mechanisms, leading to post-traumatic neuronal loss and neurological deficits. TBI-induced cell cycle activation (CCA) in post-mitotic neurons causes regulated cell death involving cyclin-dependent kinase (CDK) activation and initiation of an E2F tran...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-1156-y
更新日期:2018-11-06 00:00:00
abstract::The DNA-alkylating cytotoxic agent cyclophosphamide (CTX) is commonly used in the clinic to treat hematological malignancies like lymphomas and leukemias as well as solid tumors, but shows dose-dependent potentially life-threatening toxicities and can induce secondary malignancies. Thus, the clinical utility of CTX wo...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2017.108
更新日期:2017-03-16 00:00:00
abstract::Chemotherapy is a standard treatment for non-small-cell lung cancer (NSCLC). However, the dose-limiting toxicity of drugs and the development of chemoresistance are major clinical challenges to successful management of NSCLC. Asian traditional medicine is gaining global attention as a non-toxic alternative to chemothe...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0277-7
更新日期:2018-02-14 00:00:00
abstract::The process by which epithelial features are lost in favor of a mesenchymal phenotype is referred to as epithelial-mesenchymal transition (EMT). Most carcinomas use this mechanism to evade into neighboring tissues. Reduction or a loss of E-cadherin expression is a well-established hallmark of EMT. As a potent suppress...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2014.32
更新日期:2014-02-27 00:00:00
abstract::Homeodomain-interacting protein kinase 2 (HIPK2) is a multitalented coregulator of an increasing number of transcription factors and cofactors involved in cell death and proliferation in several organs and systems. As Hipk2(-/-) mice show behavioral abnormalities consistent with cerebellar dysfunction, we investigated...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2015.298
更新日期:2015-12-03 00:00:00
abstract::Myotonic dystrophy type 1 (DM1) is the most common type of adult muscular dystrophy caused by the expanded triple-nucleotides (CUG) repeats. Myoblast in DM1 displayed many defects, including defective myoblast differentiation, ribonuclear foci, and aberrant alternative splicing. Despite many were revealed to function ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-03112-6
更新日期:2020-10-22 00:00:00
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
更新日期:2013-04-04 00:00:00
abstract::Betulinic acid (BA) exhibits cytotoxic activity against some cancer cells. However, the molecular mechanism of BA against CRC cells was little reported. Here, we proved that BA elicited CRC cells' growth inhibition and apoptosis in a dose-dependent manner. In addition, BA treatment induced autophagy via inhibiting the...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2017.485
更新日期:2017-10-05 00:00:00
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
更新日期:2014-11-27 00:00:00
abstract::Catecholaminergic Polymorphic Ventricular Tachycardia type 2 (CPVT2) is a highly lethal recessive arrhythmogenic disease caused by mutations in the calsequestrin-2 (CASQ2) gene. We have previously demonstrated that viral transfer of the wild-type (WT) CASQ2 gene prevents the development of CPVT2 in a genetically induc...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2016.304
更新日期:2016-10-06 00:00:00
abstract::Protein tyrosine kinase 7 (PTK7) and cancer-associated fibroblasts (CAFs) play important roles in cancer stemness, respectively. However, little is known about interaction between CAFs and PTK7 in cancers. In this study, we showed that PTK7 was significantly correlated with the Wnt/β-Catenin pathway and aggressive cli...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-1116-6
更新日期:2018-10-22 00:00:00
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
更新日期:2018-02-07 00:00:00
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
更新日期:2018-06-04 00:00:00
abstract::Interleukin-8 (IL-8) expression correlates with poor prognosis in many cancers, including head and neck squamous cell carcinoma (HNSCC), but the underlying mechanism is poorly understood. In this study, we found that overexpression of IL-8 correlated with poor outcome in HNSCC patients. IL-8 significantly increased ce...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-2627-5
更新日期:2020-05-29 00:00:00
abstract::Pyroptosis is a highly inflammatory form of programmed cell death that is caused by infection with intracellular pathogens and activation of canonical or noncanonical inflammasomes. The purinergic receptor P2X7 is activated by the noncanonical inflammasome and contributes essentially to pyroptotic cell death. The Ca2+...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0373-8
更新日期:2018-02-20 00:00:00
abstract::Cigarette smoking is one of the most important and preventable risk factors for atherosclerosis. However, because of the complex composition of cigarette smoke, the detailed pathophysiological mechanisms are not fully understood. Based on controversial reports on the pro-atherogenic activity of cigarette smoke condens...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2012.162
更新日期:2012-11-15 00:00:00
abstract::Death-associated protein kinase 1 (DAPK1, DAPk, DAPK) is known for its involvement in apoptosis and autophagy-associated cell death. Here, we identified an unexpected function of DAPK1 in suppressing necroptosis. DAPK1-deficiency renders macrophages and dendritic cells susceptible to necroptotic death. We also observe...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-2534-9
更新日期:2020-05-04 00:00:00
abstract::Paracetamol (acetaminophen, APAP) is a universally used analgesic and antipyretic agent. Considered safe at therapeutic doses, overdoses cause acute liver damage characterized by centrilobular hepatic necrosis. One of the major clinical problems of paracetamol-induced liver disease is the development of hemorrhagic al...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2012.185
更新日期:2012-12-20 00:00:00
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
更新日期:2013-07-11 00:00:00