ArticleThe Journal of biological chemistry
RNA-binding proteins La and HuR cooperatively modulate translation repression of PDCD4 mRNA.
Article in The Journal of biological chemistry. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 26 citations in OpenAlex.
- Review
- Exosomal miR-373-3p Derived from Docetaxel-Resistant Lung Cancer Cells Targets PDCD4 to Promote Proliferation and Inhibit Apoptosis in Lung Cancer Cells.Biomedicines · 2026Article
- Functional characterisation of tumour suppressor PDCD4 reveals previously undisclosed role in the control of cell adhesion.Nucleic acids research · 2026Article
- ZC3H12D and DDX5 Antagonistically Regulate Cyclin D1 mRNA Stability and Cell Cycle Progression in Breast Cancer.Cancer medicine · 2025Article
- The MC4-La1 cleavage module restricts plant virus infection by integrating R-motif-mediated defense mRNA translation.Science advances · 2025Article
- Integrated pan-cancer analysis of RNA binding protein HuR investigates its biomarker potential in prognosis, immunotherapy, and drug sensitivity.PLoS computational biology · 2025Article
- The role of RNA binding proteins in cancer biology: A focus on FMRP.Genes & diseases · 2025Review
- PTBP1 knockdown impairs autophagy flux and inhibits gastric cancer progression through TXNIP-mediated oxidative stress.Cellular & molecular biology letters · 2024Article
- PDCD4 triggers α-synuclein accumulation and motor deficits via co-suppressing TFE3 and TFEB translation in a model of Parkinson's disease.NPJ Parkinson's disease · 2024Article
- An AKT1-and TRIM21-mediated phosphodegron controls proteasomal degradation of HuR enabling cell survival under heat shock.iScience · 2023Article
- p53 and HuR combinatorially control the biphasic dynamics of microRNA-125b in response to genotoxic stress.Communications biology · 2023Article
- Post-Transcriptional Control of mRNA Metabolism and Protein Secretion: The Third Level of Regulation within the NF-κB System.Biomedicines · 2022Review
- MicroRNAs, Tristetraprolin Family Members and HuR: A Complex Interplay Controlling Cancer-Related Processes.Cancers · 2022Review
- Cooperation of RNA-Binding Proteins - a Focus on Roquin Function in T Cells.Frontiers in immunology · 2022Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Posttranscriptional regulation of gene expression plays a critical role in controlling the inflammatory response. An uncontrolled inflammatory response results in chronic inflammation, often leading to tumorigenesis. Programmed cell death 4 (PDCD4) is a proinflammatory tumor-suppressor gene which helps to prevent the transition from chronic inflammation to cancer. PDCD4 mRNA translation is regulated by an interplay between the oncogenic microRNA miR-21 and the RNA-binding protein (RBP) human antigen R (HuR) in response to lipopolysaccharide stimulation, but the role of other regulatory factors remains unknown. Here, we report that the RBP lupus antigen (La) interacts with the 3'-untranslated region of PDCD4 mRNA and prevents miR-21-mediated translation repression. While lipopolysaccharide causes nuclear-cytoplasmic translocation of HuR, it enhances cellular La expression. Remarkably, La and HuR were found to bind cooperatively to the PDCD4 mRNA and mitigate miR-21-mediated translation repression. The cooperative action of La and HuR reduced cell proliferation and enhanced apoptosis, reversing the pro-oncogenic function of miR-21. Together, these observations demonstrate a cooperative interplay between two RBPs, triggered differentially by the same stimulus, which exerts a synergistic effect on PDCD4 expression and thereby helps maintain a balance between inflammation and tumorigenesis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.