Abstract:
:MicroRNAs (miRNAs) are important class of functional regulators involved in human cancers development, including colorectal cancer (CRC). Exploring aberrantly expressed miRNAs may provide us with new insights into the initiation and development of CRC by functioning as oncogenes or tumor suppressors. The aim of our study is to discover the expression pattern of miR-1249 in CRC and investigate its clinical significance as well as biological role in CRC progression. In our study, we found that miR-1249 was markedly downregulated in CRC tissues and cell lines, and negatively related to pN stage, pM stage, TNM stage, and overall survival (OS). Moreover, we demonstrated that miR-1249 was a direct transcriptional target of P53 and revealed that P53-induced miR-1249 inhibited tumor growth, metastasis and angiogenesis in vitro and vivo. Additionally, we verified that miR-1249 suppressed CRC proliferation and angiogenesis by targeting VEGFA as well as inhibited CRC metastasis by targeting both VEGFA and HMGA2. Further studying showed that miR-1249 suppressed CRC cell proliferation, migration, invasion, and angiogenesis via VEGFA-mediated Akt/mTOR pathway as well as inhibited EMT process of CRC cells by targeting both VEGFA and HMGA2. Our study indicated that P53-induced miR-1249 may suppress CRC growth, metastasis and angiogenesis by targeting VEGFA and HMGA2, as well as regulate Akt/mTOR pathway and EMT process in the initiation and development of CRC. miR-1249 might be a novel the therapeutic candidate target in CRC treatment.
journal_name
Cell Death Disjournal_title
Cell death & diseaseauthors
Chen X,Zeng K,Xu M,Liu X,Hu X,Xu T,He B,Pan Y,Sun H,Wang Sdoi
10.1038/s41419-018-1188-3subject
Has Abstractpub_date
2019-02-12 00:00:00pages
131issue
2issn
2041-4889pii
10.1038/s41419-018-1188-3journal_volume
10pub_type
杂志文章abstract::In Slavic folklore, Koschei the Immortal was bony, thin and lean. Was his condition caused by severe calorie restriction (CR)? CR deactivates the target of rapamycin pathway and slows down aging. But the life-extending effect of severe CR is limited by starvation. What if Koschei's anti-aging formula included rapamyci...
journal_title:Cell death & disease
pub_type: 杂志文章,评审
doi:10.1038/cddis.2014.520
更新日期:2014-12-04 00:00:00
abstract::Mast cells are prominent components of solid tumors and exhibit distinct phenotypes in different tumor microenvironments. However, their precise mechanism of communication in gastric cancer remains largely unclear. Here, we found that patients with GC showed a significantly higher mast cell infiltration in tumors. Mas...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-1100-1
更新日期:2018-10-10 00:00:00
abstract::Excessive fibrogenic response in the liver disrupts normal hepatic anatomy and function heralding such end-stage liver diseases as hepatocellular carcinoma and cirrhosis. Sinusoidal endothelial cells contribute to myofibroblast activation and liver fibrosis by undergoing endothelial-mesenchymal transition (EndMT). The...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-2101-4
更新日期:2019-11-27 00:00:00
abstract::The aberrant expression of long noncoding RNAs (lncRNAs) has been reported frequently in specific cancers, including high-grade serous ovarian cancer (HGSOC). The purpose of the present study was to explore the clinical significance and underlying mechanisms of a significantly dysregulated lncRNA (NEAT1) in HGSOC. Our...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0908-z
更新日期:2018-08-28 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::Colorectal cancer (CRC) is the second major cause of tumor-related deaths. MicroRNAs (miRNAs) have pivotal roles in CRC progression. Here, we describe the effect of miR-181d on CRC cell metabolism and underlying molecular mechanism. Our data firmly demonstrated that knockdown of miR-181d suppressed CRC cell proliferat...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2017.300
更新日期:2017-07-27 00:00:00
abstract::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 fib...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-1032-9
更新日期:2018-10-03 00:00:00
abstract::The ubiquitination-proteasome and degradation system is an essential process that regulates protein homeostasis. This system is involved in the regulation of cell proliferation, differentiation and survival, and dysregulations in this system lead to pathologies including cancers. The ubiquitination system is an enzyma...
journal_title:Cell death & disease
pub_type: 杂志文章,评审
doi:10.1038/cddis.2012.217
更新日期:2013-01-17 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::We demonstrate that EphB3 receptors mediate oligodendrocyte (OL) cell death in the injured spinal cord through dependence receptor mechanism. OLs in the adult spinal cord express EphB3 as well as other members of the Eph receptor family. Spinal cord injury (SCI) is associated with tissue damage, cellular loss and dist...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2015.262
更新日期:2015-10-15 00:00:00
abstract::SAM and SH3 domain-containing 1 (SASH1), a scaffold protein, is regarded as a tumor suppressor. Recent studies have verified the decreased expression of SASH1 in many tumors. Our previous clinical investigation found that SASH1 was widely expressed in normal brain tissues but reduced or absent in glioma tissues. Howev...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1645-7
更新日期:2019-05-28 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::In most clinical trials, human mesenchymal stem cells (hMSCs) are expanded in vitro before implantation. The genetic stability of human stem cells is critical for their clinical use. However, the relationship between stem-cell expansion and genetic stability is poorly understood. Here, we demonstrate that within the n...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2013.211
更新日期:2013-06-27 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::Gastric cancer (GC) is one of the most frequent malignancies, and increasing evidence supports the contribution of microRNA (miRNAs) to cancer progression. miR-1254 has been confirmed to participate in the regulation of various cancers, while the function of miR-1254 in GC remains unknown. In this study, we investigat...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-1262-x
更新日期:2019-01-10 00:00:00
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
更新日期:2010-09-23 00:00:00
abstract::Functional neuronal circuits require a constant remodeling of their network composed of highly interconnected neurons. The plasticity of synapses and the shaping of elaborated dendritic branches are energy demanding and therefore depend on an efficient mitochondrial oxidative phosphorylation (OXPHOS). The spatial and ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2014.144
更新日期:2014-04-10 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::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
更新日期:2019-02-15 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::Global cerebral ischemia/reperfusion (I/R) facilitates the activation of procaspase-3 and promotes apoptosis in hippocampus. But the mechanisms have remained uncharacterized. Protein S-nitrosylation and denitrosylation is an important reversible posttranslational modification, which is a common mechanism in signal tra...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2013.299
更新日期:2013-08-15 00:00:00
abstract::SHP2 participates in multiple signaling events by mediating T-cell development and function, and regulates cytokine-dependent granulopoiesis. To explore whether and how SHP2 can regulate bone-marrow eosinophil differentiation, we investigate the contribution of SHP2 in the bone-marrow eosinophil development in allergi...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2016.74
更新日期:2016-04-07 00:00:00
abstract::Necroptosis is an inflammatory form of programmed cell death requiring receptor-interacting protein kinase 1, 3 (RIPK1, RIPK3) and mixed lineage kinase domain-like protein (MLKL). The kinase of RIPK3 phosphorylates MLKL causing MLKL to form a pore-like structure, allowing intracellular contents to release and cell dea...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2017.20
更新日期:2017-02-02 00:00:00
abstract::The FDA-approved anti-androgen Enzalutamide (Enz) has been used successfully as the last line therapy to extend castration-resistant prostate cancer (CRPC) patients' survival by an extra 4.8 months. However, CRPC patients eventually develop Enz-resistance that may involve the induction of the androgen receptor (AR) sp...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-02970-4
更新日期:2020-11-02 00:00:00
abstract::Cannabinoids exert antiproliferative effects in a wide range of tumoral cells, including hepatocellular carcinoma (HCC) cells. In this study, we examined whether the PPARγ-activated pathway contributed to the antitumor effect of two cannabinoids, Δ9-tetrahydrocannabinol (THC) and JWH-015, against HepG2 and HUH-7 HCC c...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2013.141
更新日期:2013-05-02 00:00:00
abstract::Uncontrollable inflammatory response acts as a driver of sepsis-associated liver injury (SALI). IL-22 plays an important role in regulating inflammatory responses, but its role in SALI remains unknown. The aim of the study was to assess the association of serum IL-22 with SALI in pediatric patients and to enclose the ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-03176-4
更新日期:2020-11-11 00:00:00
abstract::Menin, encoded by the multiple endocrine neoplasia type 1 (MEN1) gene, is a tumor suppressor that leads to multiple endocrine tumors upon loss of its function. Menin functions as a transcriptional activator by tethering MLL complex to mediate histone H3 K4 methylation. It also functions as a repressor. However, the mo...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2013.98
更新日期:2013-04-11 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::Spermidine, a natural polyamine presented widely in mammalian cells, has been implicated to extend the lifespan of several model organisms by inducing autophagy. However, the effect of spermidine against neuronal damage has not yet been fully determined. In this study, neuronal cell injury was induced by treating PC12...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2017.161
更新日期:2017-04-06 00:00:00
abstract::Melatonin, an endogenous hormone molecule, has a variety of biological functions, but a functional role of melatonin in the infection of Gram-negative bacterium Vibrio vulnificus has yet to be described. In this study, we investigated the molecular mechanism of melatonin in the apoptosis of human intestinal epithelial...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-017-0083-7
更新日期:2018-01-19 00:00:00