Impact of miR-181a on SIRT1 Expression and Senescence in Hutchinson–Gilford Progeria Syndrome
Abstract
1. Introduction
2. Materials and Methods
2.1. Literature Review to Identify miRNA Implicated in the Regulation of Inflammation and Autophagy
2.2. Cell Culture
2.3. Drug and miRNA Mimic Transfection
2.4. Senescence-Associated β-Galactosidase Staining
2.5. RNA Isolation and Quality Control
2.6. Reverse Transcription
2.7. Quantitative Polymerase Chain Reaction (qPCR)
2.8. Cell Proliferation
2.9. Western Blot
2.10. Immunofluorescence
2.11. Mouse Skin qPCR Experiments
2.12. Statistics
3. Results
3.1. Text-Mining Approach to Determine miRNAs Associated with Autophagy and Inflammation
3.2. miR-181a-5p Is Upregulated in HGPS Fibroblasts During Replicative Senescence
3.3. miR-181a-5p Inhibits SIRT1 and Regulates Cell Growth and Senescence
3.4. TGFβ1 Upregulates miR-181a-5p Expression in Normal and HGPS Fibroblasts
3.5. miR-181a-5p Expression Levels Are Deregulated in a Mouse Model of HGPS
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
AMPK | 5′-AMP-activated protein kinase catalytic subunit alpha-1 |
ATG5 | Autophagy-related protein 5 |
ATM | Ataxia-telangiectasia mutated |
ATP | Adenosine-Triphosphate |
CCL2 | C-C motif chemokine ligand 2 |
cGAS | Cyclic GMP-AMP |
GAPDH | Glycerin-aldehyde-3-phosphate |
HGPS | Hutchinson–Gilford progeria syndrome |
IL-6/IL-1 | Interleukin 6/1 |
JAK | Janus Kinase |
microRNAs | miRNAs/miR |
mTOR | Mechanistic target of rapamycin |
NF-ĸB | Nuclear factor ‘kappa-light-chain-enhancer’ of activated B-cells |
PTEN | Phosphatase and tensin homolog |
RNU-6 | U6 small nuclear 1 |
ROS | Reactive oxygen species |
SASP | Senescence-associated secretory phenotype |
SIRT1 | Sirtuin 1 |
STAT | Signal transducer and activator of transcription |
STING | Stimulator of interferon genes |
TGFβ1 | Transforming growth factor β1 |
TLR | Toll-like receptor |
TNF | Tumor necrosis factor |
TRAF | TNF receptor-associated factor |
ULK1 | Unc-51-like kinase |
UTR | Untranslated region |
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Cell Strain | Abbreviation | Young Culture (Senescence Index < 5%) | Old Culture (Senescence Index > 20%) |
---|---|---|---|
GMO1582B | 1582B | Passage 10–14 | Passage 18–20 |
GMO1651c | 1651c | Passage 15–18 | Passage 23–25 |
GMO1652c | 1652c | Passage 16–19 | Passage 24–26 |
GMO3349c | 3349c | Passage 16–18 | Passage 23–26 |
GMO5565 | 5565 | Passage 14–20 | Passage 25–28 |
GMO5757c | 5757c | Passage 14–20 | Passage 25–28 |
HGADFN003 | P003 | Passage 10–15 | Passage 20–23 |
HGADFN127 | P127 | Passage 10–13 | Passage 16–19 |
HGADFN164 | P164 | Passage 10–15 | Passage 18–21 |
HGADFN178 | P178 | Passage 7–10 | Passage 12–15 |
HGADFN188 | P188 | Passage 9–12 | Passage 14–18 |
HGADFN271 | P271 | Passage 8–11 | Passage 14–16 |
HGFDFN369 | F369 | Passage 10–14 | Passage 16–18 |
HGMDFN368 | M368 | Passage 9–12 | Passage 14–16 |
Pathway | Protein | Abbreviation | Literature | Regulation |
---|---|---|---|---|
SASP | Interleukin 6 | IL-6 | [67] | Target |
Transforming growth factor β1 | TGFβ1 | [68] | Inducer | |
Energy metabolism | Sirtuin 1 | SIRT1 | [69] | Target |
Cell survival | Phosphatase and tensin homolog | PTEN | [70] | Target |
Autophagy | Autophagy-related protein 5 | ATG5 | [71] | Target |
Adenosine monophosphate-activated protein kinase | AMPK | [72] | Target | |
DNA damage | Ataxia-telangiectasia mutated | ATM | [68] | Target |
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Lederer, E.-M.; Fenzl, F.Q.; Krüger, P.; Schroll, M.; Hartinger, R.; Djabali, K. Impact of miR-181a on SIRT1 Expression and Senescence in Hutchinson–Gilford Progeria Syndrome. Diseases 2025, 13, 245. https://doi.org/10.3390/diseases13080245
Lederer E-M, Fenzl FQ, Krüger P, Schroll M, Hartinger R, Djabali K. Impact of miR-181a on SIRT1 Expression and Senescence in Hutchinson–Gilford Progeria Syndrome. Diseases. 2025; 13(8):245. https://doi.org/10.3390/diseases13080245
Chicago/Turabian StyleLederer, Eva-Maria, Felix Quirin Fenzl, Peter Krüger, Moritz Schroll, Ramona Hartinger, and Karima Djabali. 2025. "Impact of miR-181a on SIRT1 Expression and Senescence in Hutchinson–Gilford Progeria Syndrome" Diseases 13, no. 8: 245. https://doi.org/10.3390/diseases13080245
APA StyleLederer, E.-M., Fenzl, F. Q., Krüger, P., Schroll, M., Hartinger, R., & Djabali, K. (2025). Impact of miR-181a on SIRT1 Expression and Senescence in Hutchinson–Gilford Progeria Syndrome. Diseases, 13(8), 245. https://doi.org/10.3390/diseases13080245