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
- 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 - Efferocytosis plays a vital role in mitigating inflammation and subsequent tissue damage by clearing dying cells after intracerebral hemorrhage, but its underlying mechanism remains poorly understood. In this study, programmed cell death 4 (PDCD4) exhibited upregulated expression and localization to microglia following intracerebral hemorrhage. Targeted adenoviral-mediated Pdcd4 knockdown in vivo markedly improved neurological recovery and enhanced microglial efferocytosis in intracerebral hemorrhage model mice. These effects were further validated in Pdcd4 knockout mice. In an in vitro intracerebral hemorrhage model using oxyhemoglobin-treated microglia, Pdcd4 knockdown notably increased the expression of efferocytosis-related molecules AXL receptor tyrosine kinase (AXL) and MER proto-oncogene, tyrosine kinase (MERTK). Mechanistically, an interaction between PDCD4 and signal transducer and activator of transcription 3 (STAT3) identified under basal conditions was amplified following intracerebral hemorrhage. Pdcd4 knockdown also promoted Janus kinase 2 (JAK2)-mediated STAT3 phosphorylation and nuclear translocation, driving Mertk and Axl transcription to facilitate microglial efferocytosis. Furthermore, Pdcd4 knockdown markedly reduced proinflammatory factor expression while enhancing anti-inflammatory factor levels, thereby mitigating the neuronal apoptosis induced by conditioned medium. These findings indicate that PDCD4 blockade enhances microglial efferocytosis by activating the JAK2-STAT3-Mertk/Axl pathway and promotes post-intracerebral hemorrhage neurological recovery, identifying PDCD4 as a potential therapeutic target. - Source: PubMed
Publication date: 2026/04/14
Liu MengqiZai TianyuDuan ChengweiChen WeiguanZhang JiahaoZheng BaohaoZhang DongmeiLu Hongjian