ArticleEMBO reports2020
LncRNA GUARDIN suppresses cellular senescence through a LRP130-PGC1α-FOXO4-p21-dependent signaling axis.
Article in EMBO reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 21 citations in OpenAlex.
- Review
- Plasma-derived exosomes from obese knee osteoarthritis aggravate synovitis by promoting cellular senescence of synovial fibroblasts.Journal of orthopaedic translation · 2026Article
- The controversial role of senescence-associated secretory phenotype (SASP) in cancer therapy.Molecular cancer · 2025Review
- The oncogenic lncRNA MIR503HG suppresses cellular senescence counteracting supraphysiological androgen treatment in prostate cancer.Journal of experimental & clinical cancer research : CR · 2024Article
- Review
- Extracellular histones induce inflammation and senescence of vascular smooth muscle cells by activating the AMPK/FOXO4 signaling pathway.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2022Article
- Comprehensive analysis of somatic mutator-derived and immune infiltrates related lncRNA signatures of genome instability reveals potential prognostic biomarkers involved in non-small cell lung cancer.Frontiers in genetics · 2022Article
- Emerging Role of Non-Coding RNAs in Senescence.Frontiers in cell and developmental biology · 2022Review
- Relationships of Telomere Homeostasis with Oxidative Stress and Cardiac Dysfunction in Human Ischaemic Hearts.Antioxidants (Basel, Switzerland) · 2021Article
- lncRNA TRMP-S directs dual mechanisms to regulate p27-mediated cellular senescence.Molecular therapy. Nucleic acids · 2021Article
- Cellular Senescence Affects Cardiac Regeneration and Repair in Ischemic Heart Disease.Aging and disease · 2021Review
- Functional Network of the Long Non-coding RNA Growth Arrest-Specific Transcript 5 and Its Interacting Proteins in Senescence.Frontiers in genetics · 2021Article
- LncRNA GUARDIN suppresses cellular senescence through a LRP130-PGC1α-FOXO4-p21-dependent signaling axis.EMBO reports · 2020Article
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Authors and funding
8 authors at 5 institutions in 2 countries.
Funding
Abstract
The long noncoding RNA GUARDIN functions to protect genome stability. Inhibiting GUARDIN expression can alter cell fate decisions toward senescence or apoptosis, but the underlying molecular signals are unknown. Here, we show that GUARDIN is an essential component of a transcriptional repressor complex involving LRP130 and PGC1α. GUARDIN acts as a scaffold to stabilize LRP130/PGC1α heterodimers and their occupancy at the FOXO4 promotor. Destabilizing this complex by silencing of GUARDIN, LRP130, or PGC1α leads to increased expression of FOXO4 and upregulation of its target gene p21, thereby driving cells into senescence. We also found that GUARDIN expression was induced by rapamycin, an agent that suppresses cell senescence. FOS-like antigen 2 (FOSL2) acts as a transcriptional repressor of GUARDIN, and lower FOSL2 levels in response to rapamycin correlate with increased levels of GUARDIN. Together, these results demonstrate that GUARDIN inhibits p21-dependent senescence through a LRP130-PGC1α-FOXO4 signaling axis, and moreover, GUARDIN contributes to the anti-aging activities of rapamycin.
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Registered trials
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