Database for Annotation, Visualization and Integrated Discovery 2.1
National Institute of Allergy and Infectious Disease
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programmed cell death 4 (neoplastic transformation inhibitor)(PDCD4) programmed cell death 4 (neoplastic transformation inhibitor)(PDCD4) Related Genes Homo sapiens
GENERIF_SUMMARY up-regulated in senescent diploid fibroblasts, Results indicate that not only binding to eIF4A but also prevention of eIF4A binding to the MA-3 domain of eIF4Gc contributes to the mechanism by which Pdcd4 inhibits translation., overexpression of PDCD4 in carcinoid cells results in inhibition of cell proliferation., expression of pdcd4 as an indirect suppressor of CDK1/cdc2 is lost in progressed carcinomas of lung, breast, colon, and prostate, Pdcd4 suppresses tumor progression in colon carcinoma cells by the novel mechanism of down-regulating MAP4K1 transcription, with consequent inhibition of c-Jun activation and AP-1-dependent transcription., data suggest that PDCD4 is a proapoptotic molecule involved in TGF-beta1-induced apoptosis in human HCC cells, and a possible tumor suppressor in hepatocarcinogenesis, in response to mitogens, PDCD4 was rapidly phosphorylated by protein kinase S6K1 & then degraded by ubiquitin ligase SCF(betaTRCP); it is proposed that regulated degradation of PDCD4 in response to mitogens allows efficient protein synthesis & cell growth, These data suggest Pdcd4 as a new negative regulator of intravasation, and qas the invasion-related gene u-PAR. It is the first study to implicate Pdcd4 regulation of gene expression via Sp1/Sp3., Downregulation of tumor suppressor Pdcd4 promotes colonic neoplastic transformation and tumor invasion, Loss of programmed cell death 4 expression is associated with colorectal cancer, we conclude that the function of Pdcd4 might be cell type specific. A role for Pdcd4 in apoptosis or as a tumor suppressor might be limited to certain cell types., Altered cellular localization of PDCD4 when comparing normal breast to neoplastic breast tissue., Programmed Cell Death 4 (PDCD4) is regulated by microrna miR-21 and demonstrate that PDCD4 is a functionally important target for miR-21 in breast cancer cells., the PDCD4 MA3 domains compete with the eIF4G MA3 domain and RNA for eIF4A binding. PDCD4 inhibits translation initiation by displacing eIF4G and RNA from eIF4A., Pdcd4 is a translation inhibitor targeted for degradation during tumor promotion, mir-21 functions as an oncogene by a mechanism that involves translational repression of the tumor suppressor Pdcd4, Suppression of PDCD4 expression is associated with breast cancer cell invasion., results provide the first evidence that Pdcd4 is important role in the DNA-damage response and suggest that low levels of Pdcd4 expression observed in certain tumor cells contribute to tumorigenesis by affecting the fate of DNA-damaged cells, in squamous cell carcinoma lung cancer lines, alterations in Pdcd4 mRNA and protein levels are not directly linked., the pathogenesis, development and prognosis of laryngeal carcinoma maybe closely related to the high expression of PD4 and CD44v6, CD44v9 proteins., Suppression of Pdcd4 resulted in an increased release of CgA and Sg II and was accompanied by an up-regulation of intracellular PC1., PDCD4 5'CpG island methylation blocks PDCD4 expression at mRNA levels in gliomas., Inhibition of miR-21 increases endogenous levels of PDCD4 in cell line T98G and over-expression miR-21 inhibits PDCD4-dependent apoptosis, Lost or reduced PDCD4 expression is associated with the progression of ovarian serous cystadenocarcinomas and may serve as an important prognostic marker., Structural and mutational analyses reveal that Pdcd4 inhibits translation initiation by trapping eIF4A in an inactive conformation, and blocking its incorporation into the eIF4F complex., reveals insights into the inhibition mechanism of eIF4A by PDCD4 and provides a framework for designing chemicals that target eIF4A, Inhibitors of miR-21 increased levels of PDCD4 in cholangiocarcinoma., PDCD4 inhibits the malignant phenotype of ovarian cancer cells., Results indicate that HA binding to CD44 promotes PKCepsilon activation, increases the phosphorylation of the stem cell marker, Nanog, leads to microRNA-21 (miR-21) production and PDCD4 reduction., Reducing expression of miR-21 or miR-155 led to up-regulation of phosphatase and tensin homologue (PTEN), programmed cell death 4 (PDCD4), or Src homology-2 domain-containing inositol 5-phosphatase 1 (SHIP1)., Identified up-regulation of microRNA-21 (hsa-miR-21) concurrent with down-regulation of potent tumor suppressor proteins PTEN and programmed cell death 4 in cholesteatoma as compared with normal skin., miR-21 in HeLa cervical cancer cells caused profound suppression of cell proliferation, and up-regulated the expression of the tumor suppressor gene PDCD4., Study demonstrated that the loss of Pdcd4 was a common abnormality at molecular level in ovarian cancer and it might be a potential prognostic factor in ovarian cancer patients., Data show that elevated Snail expression by Pdcd4 knockdown leads to downregulation of E-cadherin resulting in activating beta-catenin/Tcf-dependent transcription., Recent findings indicate that the microRNA miR-21 posttranscriptionally regulates Pdcd4, as well as invasion, intravasation, and metastasis of colon cancer., miR-21 regulates PDCD4 expression after LPS stimulation., found that PDCD4 inhibits c-Jun amino-terminal kinase activity resulting in inhibition of the phosphorylation of c-Jun, one isoform of AP-1, PDCD4 and microRNA-21 have a role in human gastric cancer, Two isoforms of PKCs are involved in the regulation of the PDCD4 protein expression related to the proteasomal degradation pathway., The loss of Pdcd4 early in cancer progression may have an important role in the increased sensitivity of cancer cells to hypoxia through increased LOX activity and concomitant enhanced invasiveness., PDCD4 expression predicts the patient outcome in esophageal cancers., PDCD4 regulates TRAIL sensitivity in gastric cancer cells by inhibiting the PI3K/Akt signaling pathway., PDCD4 plays an important role in mediating the sensitivity of gastric cancer cells to TRAIL-induced apoptosis through FLIP suppression., Therefore, programmed cell death 4 can be an important biomarker for intraductal papillary mucinous neoplasm., data support a significant role for PDCD4 downregulation in the progression of Barrett mucosa to Barrett carcinogenesis, and confirm miR-21 as a negative regulator of PDCD4 in vivo., PDCD4 enhances cisplatin-induced apoptosis by mainly activating the death receptor pathway., Data show an association between the loss of PDCD4 expression, tumorigenesis and invasion in Oral Squamous Cell Carcinoma, and also identify a mechanism of PDCD4 down-regulation by microRNA-21 in oral carcinoma., The high expression of PD4, CD44 and PCNA proteins may be closely related to the pathogenesis, development and prognosis of laryngeal carcinoma., miR-21 expression was significantly upregulated in preneoplastic/neoplastic colon samples, consistent with PDCD4 downregulation, Our analysis of Pdcd4 expression did not reveal any significant distinction between cancerous and normal endometrium., analysis of the tandem MA-3 region of Pdcd4 protein and characterization of its interactions with eIF4A and eIF4G, PDCD4 gene is anti-oncogene that may play an important role in the pathogenesis and development of laryngeal carcinoma., this study demonstrates an inverse relationship between miR-21 and PDCD4. Which indicates that miR-21 post-transcriptionally downregulates PDCD4 by mRNA degradation through ginding to its target site with perfet complementarity., Upregulated miR-21 affects PDCD4 expression and regulates aberrant T cell responses in human SLE., c-myb mRNA as the first natural translational target mRNA of Pdcd4, Loss of heterozygosity contributes to tumor progression of oral squamous cell carcinoma, and a specific role for PDCD4, CTNNB1, and CASP4 was found., PD4 expression was elevated in laryngeal carcinoma, and might be closely related to mycoplasma infection., these results suggest that downregulation of PDCD4 expression may have an essential role in the progression and malignant proliferation of human gastrointestinal stromal tumors, PDCD4 expression was correlated with beta-catenin expression in gastric carcinoma cell lines, but not with E-cadherin, as the binding partner in the cell membrane, identified FOXO4 and PDCD4 as direct and functional targets of miR-499-5p, The low expression of PDCD4 protein is closely related to the development and progression of laryngeal squamous cell carcinoma., Data show that 4-OHT reduced PDCD4 mRNA in MCF-7 cells consistent with the increase in miR-21 induced by 4-OHT., Loss of programmed cell death 4 induces apoptosis by promoting the translation of procaspase-3 mRNA., Overexpression of miRNA-21 is associated with the biological behavior of pancreatic ductal adenocarcinoma via the downregulation of PDCD4 and TIMP3, resulting in tumor progression and an adverse clinical course., Study demonstrates that Pdcd4 is directly involved in translational suppression of a natural mRNA with a 5'-structured UTR and provides novel insight into the translational control of p53 expression., ZBP-89 is a regulator of Pdcd4 gene, binding to the basal promoter either alone or by interacting with Sp family members., These data support a decisive role for PDCD4 down regulation in transitional cell carcinoma and confirm miR-21 as a negative regulator for PDCD4., PDCD4 utilizes TIMP-2 to exert its anti-invasive effect by suppressing leptin-induced activation of extracellular signal-regulated kinases 1,2 and signal transducer and activator of transcription 3., PDCD4 is down-regulated in human RCC, which is correlated with biological aggressiveness and poor prognosis. As a tumor suppressor, PDCD4 probably plays an important role during the tumorigenesis of RCC., Data suggest that overexpression of miRNA-21 and reduced or loss of PDCD4 expression may play a role in the development and progression of gastric cancers., Ars2 is overexpressed in human cholangiocarcinoma and may be a diagnostic marker. Ars2 depletion increases PTEN and PDCD4 protein levels via the reduction of miR-21., PDCD4 mRNA levels were negatively regulated by miR-21in each tumor stage of colorectal cancer (CRC)., Data indicate that PDCD4 may play a critical function in arresting cell cycle progression at key checkpoint, thus inhibiting cell proliferation, as well as suppressing tumour metastasis., This is the first study showing a direct impact of Pdcd4 on Ang-2 levels and, thereby, angiogenesis., Suppression of tumor suppressor PDCD4 expression may be one of the important regulatory pathways of miR-21-mediated cell proliferation and decrease of apoptosis in non-small cell lung cancer., These findings suggest that ursolic acid inhibits cell growth via causing apoptosis in U251 cells by a ursolic acid-triggered TGF-beta1/miR-21/PDCD4 pathway., PDCD4 expression may play a key role in pre-cancerous lesions of human nasal inverted papillomas (NIPs) and may help predict malignant progression from benign nasal tumors to associated SCC., role of GSK3beta in Pdcd4 expression lung cancer cells, PDCD4 as a specific repressor of the internal ribosome entry site-mediated translation of antiapoptotic proteins and is regulated by S6 kinase 2 dependent translation of cellular mRNAs (such as XIAP and Bcl-x(L)) that mediate FGF-2-S6K2 prosurvival signaling and provide further insight into the role of PDCD4 in tumor suppression, IFN-dependent phosphorylation of PDCD4 results in downregulation of PDCD4 protein levels as the phosphorylated form of PDCD4 interacts with the ubiquitin ligase beta-TRCP (beta-transducin repeat-containing protein) and undergoes degradation., PDCD4 may play an important role in occurrence and development of laryngeal squamous cell carcinomas through the inducing apoptosis and inhibiting proliferation., Elevated leiomyoma miR-21 levels are predicted to decrease PDCD-4 levels, thus leiomyomas differ from other tumors where loss of PDCD-4 is associated with tumor progression., The most significant discovery of the integrated validation is the down-regulation of FABP5 and PDCD4 in KRAS-activated human tumor bronchial epithelial cells., microRNA-21 expression is up-regulated in human cholangiocarcinoma and PTEN, PDCD4 are direct effectors of microRNA-21., Pdcd4 knockdown up-regulates MAP kinase kinase kinase kinase 1 (MAP4K1) expression and increases phosphorylation of c-Jun., The data indicated that hnRNPC controls the aggressiveness of glioblastoma cells through the regulation of PDCD4. Silencing of hnRNPC lowered miR-21 levels, in turn increasing the expression of PDCD4, suppressing Akt and p70S6K activation., this study identifies a novel signaling mechanism mediated by FAT1 in regulating the activity of PDCD4 in gliomas., The present results provide evidence of PDCD4 having a role in thyroid carcino-genesis., Programmed cell death protein 4 (PDCD4) and Kruppel-like factor 6 (KLF6) were identified as critical regulators and surrogate markers of prostatic tissue architectures., PDCD4 nuclear down-regulation (which parallels miR-21 up-regulation) is involved in the molecular pathway of inflammatory bowel disease-associated carcinogenesis., PDCD4 Is Down-Regulated, Whereas miR-182 Is Up-Regulated in Ovarian Cancer, Data indicate that programmed cell death 4 (Pdcd4) knockdown altered the adhesion capacity of colon carcinoma GEO cells., The cumulative survival rate of gastric cancer patients with PDCD4 expression is significantly higher compared to the patients without PDCD4 expression., PDCD4 expression might have an essential role in the progression of salivary adenoid cystic carcinoma., Low PDCD4 is associated with tumorigenesis of liver fluke-associated cholangiocarcinoma., miR-21 promotes robust fibrogenic EMT of EMCs, in part by directly targeting PDCD4 and SPRY1., Feedback regulations of miR-21 and MAPKs via Pdcd4 and Spry1 are involved in arsenite-induced cell malignant transformation., PDCD4 negatively regulates autophagy by targeting ATG5., Loss of PDCD4 indicates chemoresistance in pancreatic cancer., miR-21 plays a necessary role in cardiac valvulogenesis, in large part due to an obligatory downregulation of PDCD4, this study reported for the first time that HBx downregulates PDCD4 and upregulates miR-21 expression, Results show that a variant MYB binding site in PDCD4 is associated to the severest form of childhood asthma suggesting that PDCD4 is a novel molecule of importance to asthmatic inflammatory responses., Data indicate that berberine could inhibit miR-21 expression and function in ovarian cancer by an enhancement of its target PDCD4, an important tumor suppressor in ovarian cancer., Findings suggest that programmed cell death 4 (PDCD4) might be a potentially valuable molecular target in diagnosis and therapy for human digestive tract cancers., Downregulation of microRNA-182 inhibits cell growth and invasion by targeting programmed cell death 4 in human lung adenocarcinoma cells., we conclude that reactive oxygen species promotes gastric carcinogenesis via upregulating miR-21 expression which in turn downregulates the expression of PDCD4 in gastric cancer cells, The expression of hMSH2 and PDCD4 in miR-21-inhibiting T98G cells., during bacterial pneumonia IFNlambda promotes inflammation by inhibiting miR-21 regulation of PDCD4., miR-21 is a key player in oncogenic EMT, its overexpression is controlled by the cooperation of genetic and epigenetic alterations, and its levels, along with ITGbeta4 and PDCD4 expression, could be exploited as a prognostic tool for CRC metastasis., PDCD4 as tumor suppressor regulated miR-184-mediated direct targeting of BCL2 and C-MYC., the miR-21/PDCD4/AP-1 autoregulatory loop is one of the main driving forces for hepatic fibrosis progression., Data suggest that the oncogenic potential of SRSF3 might be realized, in part, through the translational repression of PDCD4 mRNA., we described a novel molecular mechanism of Pdcd4 suppression in cancer cells consisting from mTOR signaling-dependent transcriptional repression of Pdcd4, PDCD4 expression may be regulated at the transcription stage as well as at the post translation stage and the transcriptional regulation occurs through the PI3K-Akt-mTOR signaling pathway in hepatoma Huh7 cells, Loss of PDCD4 expression is associated with glioblastoma., Low expression of PDCD4 protein is associated with drug resistance in advanced rectal cancer., Our data suggest that miR-21 could modulate chemosensitivity of TSCC cells to cisplatin by targeting PDCD4, and miR-21 may serve as a potential target for TSCC therapy, atheroprotective unidirectional pulsatile shear stress affects the expression of PDCD4 in endothelial cells, MicroRNA-21 may play an oncogenic role by directly targeting PDCD4 in the cellular processes of papillary thyroid carcinoma., miR-21 is overexpressed in gastric cancer and its aberrant expression may have important role in gastric cancer growth and dissemination by modulating the expression of the tumor suppressors PTEN and PDCD4, These findings suggest that the methylated form of PDCD4 promotes tumor viability during nutrient deprivation, ultimately allowing the tumor to grow more aggressively., Our results help determine the significance of Pdcd4 loss in melanoma as well as its up-regulation by Akt pathway inhibitors, When compared to controls, patients with ankylosing spondylitis had significantly higher levels of miR-21, PDCD4 mRNA, and CTX. MiR-21 expression was negatively correlated with PDCD4 in patients with AS who were taking neither NSAID nor DMARD., Down-regulation of PDCD4 s associated with cisplatin resistance in ovarian cancer., PDCD4 and miR-21 are involved in OSC oncogenesis, Data indicate that programmed cell death4 (PDCD4) is a target of microRNA-21 (miR-21)., LPS promotes PDCD4 degradation via a pathway involving PI3K and mTOR, releasing Twist2, which induces IL-10 via c-Maf., 14-3-3 binding promotes PDCD4 degradation, suggesting an important role for RSK in the inactivation of PDCD4 in melanoma., The results of the present study demonstrated that overexpression of miR-182 may be involved in chemoresistance of non-small cell lung cancer cells to cisplatin by down-regulating PDCD4., Helicobacter pylori promotes epithelial-mesenchymal transition in gastric cancer by downregulating programmed cell death protein 4 (PDCD4)., Results show that miR-21 was overexpressed in all tested head and neck squamous carcinoma cell lines, and regulated cellular proliferation possibly through downregulation of the tumor suppressor PDCD4., The study identifies poly(A)-binding protein as a novel functionally relevant Pdcd4 interaction partner that contributes to the regulation of translation by Pdcd4., Low expression of PDCD4 is associated with esophageal squamous cell carcinoma., modulation of the miR-150-PDCD4 axis shows promise as a therapeutic strategy for MIBC, increasing expression of miR-21 with consequent downregulation of the tumour suppressor gene PDCD4., In medullary thyroid carcinoma miR-21 regulates PDCD4 expression and the miR-21/PDCD4 pathway correlates with clinicopathological variables and prognosis., Data suggest that miR-183 might play an oncogenic role in esophageal squamous cell carcinoma by regulating PDCD4 expression., PDCD4 mRNA is bound by the RNA-binding proteins HuR and TIA1, resulting in modulation of PDCD4 mRNA and protein levels., Activation of p70S6K1 that is inhibited by Pdcd4 is essential for resistance to the IGF-1R inhibitor in colon tumor cells., Decreased expression of PDCD4 mRNA by miR-183 overexpression in pancreatic cancer cells was linked to cell migration and invasion., This work describes a novel mechanism of translational suppression by Pdcd4 and shows for the first time that Hipk2 controls its own synthesis by an auto-regulatory feedback mechanism., CRL3(IBTK) is a novel ubiquitin ligase with regulatory roles in cellular pathways, such as the Pdcd4-dependent translation of mRNAs, proteomic screen for paclitaxel targets not only provided novel insight into the cellular resistance to paclitaxel via the PDCD4-mitotic exit regulation axis, we demonstrate that miR-21 regulates T-cell acute lymphoblastic leukemia cell survival via repression of the tumor suppressor Pdcd4., of PDCD4 is down-regulated by HER2 signaling in AI-resistant breast cancer. Down-regulation of PDCD4 is associated with AI resistance and a poor prognosis in patients with ER-positive breast cancer., RT-qPCR and western blotting showed that miR-183 negatively regulated PDCD4 protein expression but had no impact on mRNA expression of PDCD4, PDCD4 is critical in mediating apoptosis in glioblastoma multiforme, and is downregulated by miR-21. (Review), These findings suggest that miR-21 and PDCD4 might be potential biomarkers for malignant melanoma and might provide treatment targets in the future., Unprecedentedly, HuR was also found to bind to miR-21 directly, preventing its interaction with the PDCD4 3'-UTR, thereby preventing the translation repression of PDCD4., These findings support the feasibility of future efforts for diagnosis and gene therapy for prostate cancer that are based on IL-6, miR-21, and PDCD4., Low PDCD4 increases osteosarcoma cells resistance to apoptosis., miR-21 has a role in upregulating PTEN, RECK and PDCD4 in glioma, Dysregulation of miR-21 has an important role in tumor growth and invasion by targeting PDCD4., We propose that SRSF3 could act as a coordinator of the expression of PDCD4 protein via two mechanisms on two alternatively spliced mRNA isoforms., This study describes the regulation of PDCD4 specifically in tonsil SCC by miR-499 and miR-21 and has documented the loss of PDCD4 in oropharyngeal squamous cell carcinoma, Results indicated that PDCD4 may be a novel candidate of tumor suppressor gene in hepatocellular carcinoma and that promoter hypermethylation is an important mechanism for its downregulation and a good predictor of survival., PDGF-BB stimulates cell proliferation through microRNA-21-mediated PDCD4 down-regulation, leading to the development of TAO.,
SP_COMMENT caution:The sequence shown here is derived from an Ensembl automatic analysis pipeline and should be considered as preliminary data., disease:Loss of expression correlated with tumor progression of lung and colon carcinoma., domain:Binds EIF4A1 via the MA3 domains., function:Tumor suppressor. Inhibits tumor promoter-induced neoplastic transformation. Down-regulates the expression of MAP4K1, thus inhibiting events important in driving invasion, namely, MAPK85 activation and consequent JUN-dependent transcription. May play a role in apoptosis. Inhibits the helicase activity of EIF4A and cap-dependent translation. Binds RNA., induction:IL2 stimulation inhibits expression, while IL12 increases expression., sequence caution:Contaminating sequence. Potential poly-A sequence., similarity:Belongs to the PDCD4 family., similarity:Contains 2 MI domains., subcellular location:Shuttles between the nucleus and cytoplasm. Predominantly nuclear under normal growth conditions. Exported from the nucleus in the absence of serum., subunit:Interacts with EIF4A1 and EIF4A2., tissue specificity:Up-regulated in proliferative cells. Highly expressed in epithelial cells of the mammary gland.,