AMPK-upregulated microRNA-708 plays as a suppressor of cellular senescence and aging via downregulating disabled-2 and mTORC1 activation
© 2024 The Authors. MedComm published by Sichuan International Medical Exchange & Promotion Association (SCIMEA) and John Wiley & Sons Australia, Ltd..
Senescence-associated microRNAs (SA-miRNAs) are important molecules for aging regulation. While many aging-promoting SA-miRNAs have been identified, confirmed aging-suppressive SA-miRNAs are rare, that impeded our full understanding on aging regulation. In this study, we verified that miR-708 expression is decreased in senescent cells and aged tissues and revealed that miR-708 overexpression can alleviate cellular senescence and aging performance. About the molecular cascade carrying the aging suppressive action of miR-708, we unraveled that miR-708 directly targets the 3'UTR of the disabled 2 (Dab2) gene and inhibits the expression of DAB2. Interestingly, miR-708-caused DAB2 downregulation blocks the aberrant mammalian target of rapamycin complex 1 (mTORC1) activation, a driving metabolic event for senescence progression, and restores the impaired autophagy, a downstream event of aberrant mTORC1 activation. We also found that AMP-activated protein kinase (AMPK) activation can upregulate miR-708 via the elevation of DICER expression, and miR-708 inhibitor is able to blunt the antiaging effect of AMPK. In summary, this study characterized miR-708 as an aging-suppressive SA-miRNA for the first time and uncovered a new signaling cascade, in which miR-708 links the DAB2/mTOR axis and AMPK/DICER axis together. These findings not only demonstrate the potential role of miR-708 in aging regulation, but also expand the signaling network connecting AMPK and mTORC1.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:5 |
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| Enthalten in: |
MedComm - 5(2024), 3 vom: 27. März, Seite e475 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhang, Jian [VerfasserIn] |
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| Links: |
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| Themen: |
AMP‐activated protein kinase (AMPK) |
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| Anmerkungen: |
Date Revised 12.03.2024 published: Electronic-eCollection Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1002/mco2.475 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Senescence-associated microRNAs (SA-miRNAs) are important molecules for aging regulation. While many aging-promoting SA-miRNAs have been identified, confirmed aging-suppressive SA-miRNAs are rare, that impeded our full understanding on aging regulation. In this study, we verified that miR-708 expression is decreased in senescent cells and aged tissues and revealed that miR-708 overexpression can alleviate cellular senescence and aging performance. About the molecular cascade carrying the aging suppressive action of miR-708, we unraveled that miR-708 directly targets the 3'UTR of the disabled 2 (Dab2) gene and inhibits the expression of DAB2. Interestingly, miR-708-caused DAB2 downregulation blocks the aberrant mammalian target of rapamycin complex 1 (mTORC1) activation, a driving metabolic event for senescence progression, and restores the impaired autophagy, a downstream event of aberrant mTORC1 activation. We also found that AMP-activated protein kinase (AMPK) activation can upregulate miR-708 via the elevation of DICER expression, and miR-708 inhibitor is able to blunt the antiaging effect of AMPK. In summary, this study characterized miR-708 as an aging-suppressive SA-miRNA for the first time and uncovered a new signaling cascade, in which miR-708 links the DAB2/mTOR axis and AMPK/DICER axis together. These findings not only demonstrate the potential role of miR-708 in aging regulation, but also expand the signaling network connecting AMPK and mTORC1 | ||
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| 650 | 4 | |a AMP‐activated protein kinase (AMPK) | |
| 650 | 4 | |a Disabled 2 (DAB2) | |
| 650 | 4 | |a aging | |
| 650 | 4 | |a mammalian traget of rapamycin coplex 1 (mTORC1) | |
| 650 | 4 | |a miR‐708 | |
| 700 | 1 | |a Gong, Hui |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Tingting |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Weitong |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Honghan |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Tiepeng |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Yu |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Ming |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Ning |e verfasserin |4 aut | |
| 700 | 1 | |a Gong, Chuhui |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Fangfang |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Cuiying |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Jin |e verfasserin |4 aut | |
| 700 | 1 | |a Xiao, Hengyi |e verfasserin |4 aut | |
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