title: MiR-23a-depressed autophagy is a participant in PUVA- and UVB-induced premature senescence.
abstract: Autophagy is a cellular catabolic mechanism that is activated in response to stress conditions, including ultraviolet (UV) irradiation, starvation, and misfolded protein accumulation. Abnormalities in autophagy are associated with several pathologies, including aging and cancer. Furthermore, recent studies have demonstrated that microRNAs (miRNAs) are potent modulators of the autophagy pathway. As a result, the current study aims to elucidate the role of the autophagy-related miRNA miR-23ain the process of photoaging. Experiments demonstrated that the antagomir-mediated inactivation of miR-23a resulted in the stimulation of PUVA- and UVB-depressed autophagy flux and protected human fibroblasts from premature senescence. Furthermore, AMBRA1 was identified as a miR-23a target. AMBRA1 cellular levels increased following the introduction of miR-23a antagomirs. And a bioinformatics analysis revealed that the AMBRA1 3' UTR contains functional miR-23a responsive sequences. Finally, it was also demonstrated that both AMBRA1 overexpression and Rapamycin treatment were both able to rescue fibroblasts from PUVA and UVB irradiation-induced autophagy inhibition, but that these effects could also be mitigated by miR-23a overexpression. Therefore, this study concludes that miR-23a-regulated autophagy is a novel and important regulator of ultraviolet-induced premature senescence and AMBRA1 is a rate-limiting miRNA target in this pathway.
authors.affiliation: Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Jia-An
authors.initials: JA
authors.lastname: Zhang
authors.affiliation: Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.|Jiangsu Provincial Key Laboratory of Molecular Biology for Skin Diseases and STIs, Nanjing, Jiangsu, China.
authors.forename: Bing-Rong
authors.initials: BR
authors.lastname: Zhou
authors.affiliation: Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Jiangsu Provincial Key Laboratory of Molecular Biology for Skin Diseases and STIs, Nanjing, Jiangsu, China.|Institute of Dermatology, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Nanjing, Jiangsu, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Maya
authors.initials: M
authors.lastname: Gozali
authors.affiliation: Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Di
authors.initials: D
authors.lastname: Wu
authors.affiliation: Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Zhi-Qiang
authors.initials: ZQ
authors.lastname: Yin
authors.affiliation: Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Luo
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D000070416:Antagomirs / Q000235:genetics; D001343:Autophagy / Q000235:genetics; D016922:Cellular Senescence / Q000235:genetics / Q000528:radiation effects; D005347:Fibroblasts / Q000473:pathology / Q000528:radiation effects; D006801:Humans; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D012867:Skin / Q000528:radiation effects; D015595:Skin Aging / Q000235:genetics* / Q000473:pathology; D012879:Skin Physiological Phenomena / Q000528:radiation effects; D014162:Transfection
chemical_list: C553334:AMBRA1 protein, human; D048868:Adaptor Proteins, Signal Transducing; D000070416:Antagomirs; C552430:MIRN23a microRNA, human; D035683:MicroRNAs
keywords: AMBRA1; Gerotarget; autophagy; miR-23a; stress-induced premature senescence; ultraviolet