Ask about this productRelated genes to: PDCD4 antibody
- Gene:
- PDCD4 NIH gene
- Name:
- programmed cell death 4
- Previous symbol:
- -
- Synonyms:
- H731
- Chromosome:
- 10q25.2
- Locus Type:
- gene with protein product
- Date approved:
- 2000-05-10
- Date modifiied:
- 2016-11-30
Related products to: PDCD4 antibody
Related articles to: PDCD4 antibody
- Programmed cell death 4 (Pdcd4) is a well-established tumor suppressor and inhibitor of protein translation. Although Pdcd4-mediated translational repression contributes to tumor suppression, emerging evidence suggests that Pdcd4 also exerts translation-independent functions. In this study, we found that Pdcd4 suppresses tumorigenesis through direct interaction with the rapamycin-insensitive companion of mTOR (Rictor), a core component of the mTORC2 complex. Using deletion mapping and site-directed mutagenesis, we defined the Rictor-binding domain of Pdcd4 and identified three critical residues, R105, K108, and R110, for this interaction. Co-immunoprecipitation and in vitro kinase assays demonstrated that Pdcd4 binding to Rictor disrupted mTORC2 complex assembly and inhibited its kinase activity. Reverse phase protein array analysis revealed that 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3), a key regulator of glycolysis, was markedly upregulated in Pdcd4-knockdown cells. Restoration of wild-type Pdcd4, but not a Rictor-binding-deficient mutant, reduced PFKFB3 protein abundance by promoting ubiquitin-proteasome-mediated degradation. Functionally, Pdcd4-Rictor interaction suppressed glycolytic activity and inhibited tumor cell proliferation in cultured cells and xenograft models. Consistent with these findings, non-small cell lung cancer (NSCLC) tissues exhibited significantly elevated protein levels of Rictor and PFKFB3 compared with adjacent normal tissues, with a positive correlation between their expression. Collectively, these results demonstrate that the translation-independent mechanism by which Pdcd4 disrupts mTORC2 signaling and downregulates PFKFB3 plays a critical role in suppressing NSCLC growth and glycolysis. - Source: PubMed
Publication date: 2026/04/22
Yang Hsin-ShengWang QingXin YumengZokaei ElhamZeng LiangPiecoro Dava WestChen MinZhang YanquanYang KatieWang ChiLiu Xiaoqi - Pancreatic ductal adenocarcinoma remains one of the most lethal malignancies with only an 11% 5-year survival rate. Oncogenic microRNAs (miRNA), particularly miR-21, miR-155, and miR-18a, drive tumor progression by silencing tumor suppressors and promoting chemoresistance. Single-target miRNA inhibition has shown limited clinical efficacy because of complex network redundancy and compensatory pathway activation, necessitating multitarget therapeutic approaches. We designed and validated a trispecific miRNA sponge construct containing high-affinity target sites for all 3 oncomiRs, demonstrated in silico through miRNAsong analysis with an approximately 11-kcal/mol thermodynamic specificity gap relative to off-targets. The sponge was functionally tested in the human pancreatic ductal adenocarcinoma cell lines PANC-1 and AsPC-1 using comprehensive assays including dual-luciferase reporter, quantitative reverse transcription polymerase chain reaction, flow cytometry-based apoptosis analysis, scratch-wound migration, and gemcitabine chemosensitization studies. In AsPC-1 cells, the trispecific sponge achieved 99.0%-99.9% silencing of target miRNAs and 349-fold reporter reduction, inducing a 6.1-fold increase in apoptosis and approximately 44% reduction in wound closure at 72 hours compared with nontargeting controls. PANC-1 cells showed moderate but significant responses with 65%-98% miRNA silencing, a 2.2-fold increase in apoptosis, and approximately 51% reduction in wound closure at 72 hours under identical assay conditions. Mechanistically, simultaneous miRNA inhibition synergistically reactivated tumor suppressor genes PDCD4, ESR1, and NOTCH2 (6.3-7.7-fold upregulation) and sensitized chemoresistant cells to gemcitabine by 1.5- to 1.8-fold. Across the evaluated functional endpoints, the trispecific sponge conferred approximately 1.2- to 95-fold changes relative to the nontargeting control and, in many instances, elicited equal or greater effects than single-target constructs, consistent with a broader network-level impact rather than uniform superiority in every assay. This platform represents a promising strategy for pancreatic ductal adenocarcinoma therapy warranting preclinical development and clinical translation. SIGNIFICANCE STATEMENT: Pancreatic cancer chemoresistance drives poor survival. The trispecific microRNA sponge simultaneously targets miR-21, miR-155, and miR-18a, synergistically reactivating tumor suppressors and enhancing gemcitabine efficacy more than single-target approaches. This multitarget microRNA strategy represents a novel therapeutic platform for overcoming chemoresistance in pancreatic cancer. - Source: PubMed
Publication date: 2026/03/31
Karimi MahdiMotamed NasrinShafizadeh AlirezaMardani PedramArefian Ehsan - Objective MicroRNAs (miRNAs) are small endogenous single-stranded non-coding RNAs, approximately 20-25 nucleotides in length, that regulate the expression of potential target mRNAs at the post-transcriptional level. miRNAs are abnormally expressed in many malignant tumors, and are closely associated with tumorigenesis and development, functioning either as proto-oncogenes or oncogenes. Studies have revealed that microRNA-21 (miR-21) is one of the most common oncogenes across various cancer types. However, the function of miR-21 in osteosarcoma has not been fully elucidated. This study aims to investigate the effect of miR-21 on the proliferation, invasion and apoptosis of osteosarcoma cell line MG63 and its underlying mechanisms. Methods Bioinformatics was used to predict the potential target genes of miR-21. The expression levels of miR-21 and programmed cell death 4 (PDCD4) in osteosarcoma cell line MG63 were measured by qRT-PCR and Western blot, respectively. After the expression of miR-21 was regulated (either up-regulated or inhibited), its biological effects on cell viability, cell cycle progression and apoptosis were assessed. The targeting relationship between miR-21 and PDCD4 was verified by using dual-luciferase reporter gene assay. Results Bioinformatics prediction showed that the 3'-UTR region of human PDCD4 gene contained multiple potential miRNA target sites. qRT-PCR results showed that the expression level of miR-21 in the pcDNA3.1-miR-21 group was significantly higher than that in the pcDNA3.1 group and the blank group. Compared with the blank group, up-regulation of miR-21 significantly promoted the proliferation and invasion of osteosarcoma MG63 cells, while inhibiting cell apoptosis. Luciferase reporter gene assay confirmed that PDCD4 was a direct target gene of miR-21, and there was a negative correlation between miR-21 and PDCD4. Conclusion Up-regulation of miR-21 expression promotes proliferation and invasion while inhibiting apoptosis of osteosarcoma cell line MG63 by suppressing the level of endogenous PDCD4. In contrast, down-regulation of miR-21 expression inhibits proliferation and invasion while promoting apoptosis of osteosarcoma cell line MG63. Therefore, miR-21 functions as an oncogene in the development of osteosarcoma and could be a potential therapeutic target. - Source: PubMed
Wang ZhipengZhang ZiruZhao Jian - Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality worldwide, and tumors harboring p53 mutations have limited therapeutic options. Chronic inflammation and microRNA dysregulation are key drivers of NSCLC progression, yet their coordinated therapeutic targeting remains poorly understood. This study aimed to evaluate whether a novel therapeutic combination of colchicine (Col) and rosiglitazone (Rosi) can modulate hsa-miRNA-26a-5p and hsa-miRNA-21-5p and influence IL-6/STAT3/axis-driven oncogenic signaling in NSCLC, particularly under inflammatory conditions. Given the central role of p53 gene in controlling cellular response to therapy, we investigated the role of mutant p53 vs wild-type in response to the individual and combined treatment of Col/Rosi in two NSCLC cell lines, A549 (p53-wild-type) and NCI-H358 (p53-null, transfected with p53-R273H mutant), using WST-1 viability assays, caspase-3 and PARP1 assays, western blotting, and RT-qPCR analysis of key miRNAs. In silico modeling and transcriptomic data from lung adenocarcinoma patients were used to support mechanistic and clinical relevance. In p53-R273H-mutant NCI-H358 cells, the Col/Rosi treatment synergistically reduced viability and induced apoptosis more effectively than either agent alone. This effect was associated with upregulation of the tumor-suppressor hsa-miRNA-26a-5p, suppression of oncogenic hsa-miRNA-21-5p, restoration of PTEN, PDCD4, and LIN28B, and inhibition of the IL-6/STAT3/NF-κB axis, consistent with patient-derived datasets. In contrast, p53-wild-type A549 cells exhibited an antagonistic response. This study identifies a genotype-dependent therapeutic interaction between Col and Rosi and demonstrates that reprogramming of hsa-miRNA-26a-5p and hsa-miRNA-21-5p constitutes a central mechanism underlying their anti-tumor and anti-inflammatory effects in NSCLC, particularly in p53-R273H-mutant NCI-H358 cells compared with p53-wild-type cells. The findings highlight the need for further investigation into the Col/Rosi combination for inflammation-related lung cancer and p53 expression. In vitro studies and bioinformatics analyses suggest a miRNA-associated regulatory mechanism that could guide future research. - Source: PubMed
Publication date: 2026/04/21
Younes NayeraSadek OmaymaSultan Ahmed - The PDCD4 (programmed cell death protein 4) protein is a key target protein, in particular for the well-studied miR-21. By suppressing its synthesis, miR-21 exerts its influence on key cellular biological processes. Furthermore, miR-21 itself is one of the most relevant predictor markers for assessing the risk of developing gastric cancer. - Source: PubMed
Kononov A VRubtsov V APomorgailo E GMozgovoi S IShimanskaya A GMarkelova M V