AMPK‐upregulated microRNA‐708 plays as a suppressor of cellular senescence and aging via downregulating disabled‐2 and mTORC1 activation
Abstract 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‐7...
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| Format: | Article |
| Language: | English |
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Wiley
2024-03-01
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| Series: | MedComm |
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| Online Access: | https://doi.org/10.1002/mco2.475 |
| _version_ | 1797231430996066304 |
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| author | Jian Zhang Hui Gong Tingting Zhao Weitong Xu Honghan Chen Tiepeng Li Yu Yang Ming Yang Ning Huang Chuhui Gong Fangfang Wang Cuiying Zhang Jin Liu Hengyi Xiao |
| author_facet | Jian Zhang Hui Gong Tingting Zhao Weitong Xu Honghan Chen Tiepeng Li Yu Yang Ming Yang Ning Huang Chuhui Gong Fangfang Wang Cuiying Zhang Jin Liu Hengyi Xiao |
| author_sort | Jian Zhang |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-04-24T15:44:16Z |
| format | Article |
| id | doaj.art-d69463e9705548748608c83cb797c9a5 |
| institution | Directory Open Access Journal |
| issn | 2688-2663 |
| language | English |
| last_indexed | 2024-04-24T15:44:16Z |
| publishDate | 2024-03-01 |
| publisher | Wiley |
| record_format | Article |
| series | MedComm |
| spelling | doaj.art-d69463e9705548748608c83cb797c9a52024-04-01T16:35:35ZengWileyMedComm2688-26632024-03-0153n/an/a10.1002/mco2.475AMPK‐upregulated microRNA‐708 plays as a suppressor of cellular senescence and aging via downregulating disabled‐2 and mTORC1 activationJian Zhang0Hui Gong1Tingting Zhao2Weitong Xu3Honghan Chen4Tiepeng Li5Yu Yang6Ming Yang7Ning Huang8Chuhui Gong9Fangfang Wang10Cuiying Zhang11Jin Liu12Hengyi Xiao13The Department of Aging and Geriatric MedicineNational Clinical Research Center for GeriatricsState Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu ChinaThe Department of Aging and Geriatric MedicineNational Clinical Research Center for GeriatricsState Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu ChinaThe Department of Aging and Geriatric MedicineNational Clinical Research Center for GeriatricsState Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu ChinaThe Department of Aging and Geriatric MedicineNational Clinical Research Center for GeriatricsState Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu ChinaThe Department of Aging and Geriatric MedicineNational Clinical Research Center for GeriatricsState Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu ChinaThe Department of Aging and Geriatric MedicineNational Clinical Research Center for GeriatricsState Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu ChinaThe Department of Aging and Geriatric MedicineNational Clinical Research Center for GeriatricsState Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu ChinaThe Department of Aging and Geriatric MedicineNational Clinical Research Center for GeriatricsState Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu ChinaThe Department of Aging and Geriatric MedicineNational Clinical Research Center for GeriatricsState Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu ChinaThe Department of Aging and Geriatric MedicineNational Clinical Research Center for GeriatricsState Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu ChinaThe Department of Aging and Geriatric MedicineNational Clinical Research Center for GeriatricsState Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu ChinaDepartment of Laboratory Medicine The Second People's Hospital of Changzhi City Changzhi ChinaThe Department of Aging and Geriatric MedicineNational Clinical Research Center for GeriatricsState Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu ChinaThe Department of Aging and Geriatric MedicineNational Clinical Research Center for GeriatricsState Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu ChinaAbstract 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.https://doi.org/10.1002/mco2.475agingAMP‐activated protein kinase (AMPK)Disabled 2 (DAB2)miR‐708mammalian traget of rapamycin coplex 1 (mTORC1) |
| spellingShingle | Jian Zhang Hui Gong Tingting Zhao Weitong Xu Honghan Chen Tiepeng Li Yu Yang Ming Yang Ning Huang Chuhui Gong Fangfang Wang Cuiying Zhang Jin Liu Hengyi Xiao AMPK‐upregulated microRNA‐708 plays as a suppressor of cellular senescence and aging via downregulating disabled‐2 and mTORC1 activation MedComm aging AMP‐activated protein kinase (AMPK) Disabled 2 (DAB2) miR‐708 mammalian traget of rapamycin coplex 1 (mTORC1) |
| title | AMPK‐upregulated microRNA‐708 plays as a suppressor of cellular senescence and aging via downregulating disabled‐2 and mTORC1 activation |
| title_full | AMPK‐upregulated microRNA‐708 plays as a suppressor of cellular senescence and aging via downregulating disabled‐2 and mTORC1 activation |
| title_fullStr | AMPK‐upregulated microRNA‐708 plays as a suppressor of cellular senescence and aging via downregulating disabled‐2 and mTORC1 activation |
| title_full_unstemmed | AMPK‐upregulated microRNA‐708 plays as a suppressor of cellular senescence and aging via downregulating disabled‐2 and mTORC1 activation |
| title_short | AMPK‐upregulated microRNA‐708 plays as a suppressor of cellular senescence and aging via downregulating disabled‐2 and mTORC1 activation |
| title_sort | ampk upregulated microrna 708 plays as a suppressor of cellular senescence and aging via downregulating disabled 2 and mtorc1 activation |
| topic | aging AMP‐activated protein kinase (AMPK) Disabled 2 (DAB2) miR‐708 mammalian traget of rapamycin coplex 1 (mTORC1) |
| url | https://doi.org/10.1002/mco2.475 |
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