MiR-23a-depressed autophagy is a participant in PUVA- and UVB-induced premature senescence.
MiR-23a-depressed autophagy is a participant in PUVA- and UVB-induced premature senescence.
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MiR-23a 抑制的自噬参与了 PUVA 和 UVB 诱导的过早衰老
DOI：
10.18632/oncotarget.9357
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发表时间：
2016-06-21
期刊：
影响因子：
--
通讯作者：
Luo D
中科院分区：
文献类型：
--
作者：
Zhang JA;Zhou BR;Xu Y;Chen X;Liu J;Gozali M;Wu D;Yin ZQ;Luo D
自噬是一种细胞分解代谢机制，其响应于应激条件而被激活，包括紫外线（UV）照射、饥饿和错误折叠的蛋白质积累。自噬的抑制与几种病理学有关，包括衰老和癌症。此外，最近的研究表明，microRNAs（miRNAs）是自噬途径的有效调节剂。因此，本研究旨在阐明自噬相关miRNA miR-23在光老化过程中的作用。实验证明，阿替洛尔介导的miR-23 a失活导致PUVA和UVB抑制的自噬通量的刺激，并保护人成纤维细胞免于过早衰老。此外，AMBRA 1被鉴定为miR-23 a靶标。AMBRA 1细胞水平在引入miR-23 a引物后增加。生物信息学分析表明，AMBRA 1 3′ UTR含有miR-23 a应答序列。最后，还证明了AMBRA 1过表达和雷帕霉素处理都能够从PUVA和UVB辐射诱导的自噬抑制中拯救成纤维细胞，但是这些作用也可以通过miR-23 a过表达来减轻。因此，本研究得出结论，miR-23 a调节的自噬是紫外线诱导的早衰的一种新的和重要的调节剂，AMBRA 1是该途径中的限速miRNA靶点。
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.
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影响因子：
6.6
作者：
Fiedler, Jan;Stoehr, Andrea;Thum, Thomas
通讯作者：
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影响因子：
64.8
作者：
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DOI：
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发表时间：
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期刊：
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影响因子：
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作者：
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通讯作者：
Gilchrest, Barbara A
影响因子：
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作者：
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通讯作者：
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