Abstract:
:Our recent study identified a list of differentially expressed microRNAs (miRNAs) in human prostate cancer (PCa) tissues compared to adjacent benign prostate tissues. In the current study, to identify the crucial miRNA-mRNA regulatory biomodule involved into prostate carcinogenesis based on the previous miRNA expression profile in PCa, we proposed an integrated systematic approach which combined miRNA-mediated gene expression regulatory network analysis, experimental validations in vitro and in vivo, as well as clinical significance evaluation. As a result, the CCND1-RNASEL-CDKN1A-TP73-MDM2-UBE2I axis was identified as a bottleneck in the miRNA-mediated gene expression regulatory network of PCa according to network topological analysis. The direct binding relationship between TP73 and PCa downregulated miR-193a-5p, and the direct binding relationship between UBE2I and PCa upregulated miR-188-5p were both experimentally validated. In addition, miR-193a-5p had a more significant regulatory effect on the tumor promoter isoform of TP73-deltaNp73 than on the tumor suppressive isoform of TP73-TAp73. Importantly, the deregulation of either the miR-193a-5p-TP73 or miR-188-5p-UBE2I axes was significantly associated with aggressive progression and poor prognosis in PCa patients. Gain- and loss-of-function experiments showed that miR-193a-5p efficiently inhibited in vitro PCa cell proliferation, migration, and invasion, and in vivo tumor growth, and markedly induced PCa cell apoptosis via regulating TP73 with a corresponding suppression of the CCND1-RNASEL-CDKN1A-MDM2 axis. In contrast, miR-188-5p exerted its tumor promoter roles through targeting UBE2I with a subsequent activation of the CCND1-RNASEL-CDKN1A-MDM2 axis. Taken together, this integrated analysis revealed the potential roles of the miR-193a-5p/TP73 and miR-188-5p/UBE2i negative regulation pairs in PCa. In addition to the significant clinical relevance, miR-193a-5p- and miR-188-5p-regulated CCND1-RNASEL-CDKN1A-TP73-MDM2-UBE2I signaling may be a novel regulatory biomodule in prostate carcinogenesis.
journal_name
Cell Death Disjournal_title
Cell death & diseaseauthors
Zhang Y,Jiang F,He H,Ye J,Mao X,Guo Q,Wu SL,Zhong W,Wu CL,Lin Ndoi
10.1038/s41419-018-0293-7subject
Has Abstractpub_date
2018-02-21 00:00:00pages
301issue
3issn
2041-4889pii
10.1038/s41419-018-0293-7journal_volume
9pub_type
杂志文章abstract::In the healthcare sector, phytocompounds are known to be beneficial by contributing or alleviating a variety of diseases. Studies have demonstrated the progressive effects of phytocompounds on immune-related diseases and to exhibit anticancer effects. Graviola tree is an evergreen tree with its extracts (leafs and see...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0772-x
更新日期:2018-07-09 00:00:00
abstract::Kidney aging leads to an increased incidence of end-stage renal disease (ESRD) in the elderly, and aging is a complex biological process controlled by signaling pathways and transcription factors. Podocyte senescence plays a central role in injury resulting from kidney aging. Here, we demonstrated the critical role of...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1933-2
更新日期:2019-09-17 00:00:00
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
doi:10.1038/s41419-018-0561-6
更新日期:2018-05-01 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::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
更新日期:2015-06-11 00:00:00
abstract::African swine fever virus (ASFV) infection induces apoptosis in the infected cell; however, the consequences of this activation on virus replication have not been defined. In order to identify the role of apoptosis in ASFV infection, we analyzed caspase induction during the infection and the impact of caspase inhibiti...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2012.81
更新日期:2012-07-05 00:00:00
abstract::Osteoclasts are absorptive cells that play a critical role in homeostatic bone remodeling and pathological bone resorption. Emerging evidence suggests an important role of epigenetic regulation in osteoclastogenesis. In this study, we investigated the role of DOT1L, which regulates gene expression epigenetically by hi...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-017-0040-5
更新日期:2018-01-18 00:00:00
abstract::Plastic phenotype convention between glioma stem cells (GSCs) and non-stem tumor cells (NSTCs) significantly fuels glioblastoma heterogeneity that causes therapeutic failure. Recent progressions indicate that glucose metabolic reprogramming could drive cell fates. However, the metabolic pattern of GSCs and NSTCs and i...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-1015-x
更新日期:2018-09-24 00:00:00
abstract::Obesity-related kidney diseases are becoming serious health problems worldwide, yet the mechanism by which obesity causes kidney injury is not fully understood. The purpose of current study was to investigate the role of Mas receptor in lipid-induced kidney injury. In mice fed with high-fat diet (HFD), the protein abu...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-03375-z
更新日期:2021-01-21 00:00:00
abstract::In renal cell carcinoma, transglutaminase 2 (TGase 2) crosslinks p53 in autophagosomes, resulting in p53 depletion and the tumor's evasion of apoptosis. Inhibition of TGase 2 stabilizes p53 and induces tumor cells to enter apoptosis. This study explored the mechanism of TGase 2-dependent p53 degradation. We found that...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2016.14
更新日期:2016-03-31 00:00:00
abstract::Chemotherapy failure is the major cause of recurrence and poor prognosis in colorectal cancer (CRC) patients. The role of the differentially expressed lncRNAs in 5-Fluorouracil chemoresistance has not fully explained. Here, we observed lncRNA H19 was associated with the 5-Fu resistance in CRC. Quantitative analysis in...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-1187-4
更新日期:2018-11-19 00:00:00
abstract::Aberrant de novo lipogenesis (DNL) results in excessive hepatic lipid accumulation and liver steatosis, the causative factors of many liver diseases, such as non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), and hepatocellular carcinoma (HCC). However, the underlying mechanism of DNL dys...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-03075-8
更新日期:2020-10-10 00:00:00
abstract::Numerous evidences have shown that circular RNAs (circRNAs) play a key role in regulating the pathogenesis of cancer. However, the mechanism of circRNAs in urothelial carcinoma of bladder (UCB) remains largely unclear. In this study, we found circFAM114A2 was significantly downregulated both in UCB tissue specimens an...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-2226-5
更新日期:2020-01-22 00:00:00
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
doi:10.1038/s41419-020-02800-7
更新日期:2020-08-21 00:00:00
abstract::Erythropoietin (EPO) is an evolutionarily conserved hormone well documented for its erythropoietic role via binding the homodimeric EPO receptor (EPOR)2. In past decades, evidence has proved that EPO acts far beyond erythropoiesis. By binding the tissue-protective receptor (TPR), EPO suppresses proinflammatory cytokin...
journal_title:Cell death & disease
pub_type: 杂志文章,评审
doi:10.1038/s41419-020-2276-8
更新日期:2020-02-03 00:00:00
abstract::Pancreatic ductal adenocarcinoma, an aggressively invasive, treatment-resistant malignancy and the fourth leading cause of cancer deaths in the United States, is usually detectable only when already inevitably fatal. Despite advances in genetic screening, mapping and molecular characterization, its pathology remains l...
journal_title:Cell death & disease
pub_type: 杂志文章,评审
doi:10.1038/cddis.2014.38
更新日期:2014-02-20 00:00:00
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
doi:10.1038/cddis.2012.179
更新日期:2012-12-06 00:00:00
abstract::Immune surveillance through Foxp3+ regulatory T cells plays a crucial role in bone homeostasis. Scurfy, the mouse model of autoimmune IPEX syndrome, bears a loss-of-function mutation in Foxp3 that leads to multi-organ inflammation. Herein, we report that scurfy mice exhibit severe bone loss mediated by accelerated ost...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2015.87
更新日期:2015-04-16 00:00:00
abstract::Cytotoxic T lymphocytes (CTL) and natural killer cells (NK)-mediated elimination of tumor cells is mostly dependent on Granzyme B apoptotic pathway, which is regulated by the wild type (wt) p53 protein. Because TP53 inactivating mutations, frequently found in human tumors, could interfere with Granzyme B-mediated cell...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1950-1
更新日期:2019-09-20 00:00:00
abstract::New bone anabolic agents for the effective treatment of bone metabolic diseases like osteoporosis are of high clinical demand. In the present study, we reveal the function of salt-inducible kinase 1 (SIK1) in regulating osteoblast differentiation. Gene knockdown of SIK1 but not of SIK2 or SIK3 expression in primary pr...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1915-4
更新日期:2019-10-31 00:00:00
abstract::Detailed understanding of the mechanistic steps underlying tumor initiation and malignant progression is critical for insights of potentially novel therapeutic modalities. Cellular reprogramming is an approach of particular interest because it can provide a means to reset the differentiation state of the cancer cells ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2016.189
更新日期:2016-07-28 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::Due to limited treatment options, pre-eclampsia (PE) is associated with fetal perinatal and maternal morbidity and mortality. During the causes of PE, failure of uterine spiral artery remodeling which might be related to functioning abnormally of trophoblast cells, result in the occurrence and progression of PE. Recen...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2017.503
更新日期:2017-10-12 00:00:00
abstract::The mitogen-activated protein kinase (MAPK) pathway has been shown to be involved in both neurodevelopment and neurodegeneration. c-Jun N-terminal kinase (JNK), a MAPK important in retinal development and after optic nerve crush injury, is regulated by two upstream kinases: MKK4 and MKK7. The specific requirements of ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-1079-7
更新日期:2018-10-26 00:00:00
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
更新日期:2020-05-19 00:00:00
abstract::The injurious consequences of ionizing radiation (IR) to normal human cells and the acquired radioresistance of cancer cells represent limitations to cancer radiotherapy. IR induces DNA damage response pathways that orchestrate cell cycle arrest, DNA repair or apoptosis such that irradiated cells are either repaired o...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2011.3
更新日期:2011-02-10 00:00:00
abstract::Nutlin-3 selectively activates p53 by inhibiting the interaction of this tumor suppressor with its negative regulator murine double minute 2 (mdm2), while trichostatin A (TSA) is one of the most potent histone deacetylase (HDAC) inhibitors currently available. As both Nutlin-3 and TSA increase the levels of the cell c...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2013.61
更新日期:2013-03-07 00:00:00
abstract::Following publication of this article, it was brought to our attention that there was a typo in the References (reference number 43) whereby the first author's name was misspelled. The correct citation is provided below. We apologize for the inconvenience. ...
journal_title:Cell death & disease
pub_type: 已发布勘误
doi:10.1038/s41419-019-2029-8
更新日期:2019-10-22 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::Accumulating evidences indicate that microRNAs (miRNAs) play vital roles in multiple diseases, including cancer. In the present study, we showed that miR-6775-3p plays a tumor suppressive role in esophageal squamous cell carcinoma (ESCC). High expression miR-6775-3p is associated with good clinical outcomes of ESCC pa...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-1119-3
更新日期:2018-10-17 00:00:00