Oxidative stress dependent microRNA-34a activation via PI3Kα reduces the expression of sirtuin-1 and sirtuin-6 in epithelial cells.
Oxidative stress dependent microRNA-34a activation via PI3Kα reduces the expression of sirtuin-1 and sirtuin-6 in epithelial cells.
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DOI：
10.1038/srep35871
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发表时间：
2016-10-21
影响因子：
4.6
通讯作者：
Barnes PJ
中科院分区：
文献类型：
--
作者：
Baker JR;Vuppusetty C;Colley T;Papaioannou AI;Fenwick P;Donnelly L;Ito K;Barnes PJ
Sirtuin-1 (SIRT1) and SIRT6, NAD+-dependent Class III protein deacetylases, are putative anti-aging enzymes, down-regulated in patients with chronic obstructive pulmonary disease (COPD), which is characterized by the accelerated ageing of the lung and associated with increased oxidative stress. Here, we show that oxidative stress (hydrogen peroxide) selectively elevates microRNA-34a (miR-34a) but not the related miR-34b/c, with concomitant reduction of SIRT1/-6 in bronchial epithelial cells (BEAS2B), which was also observed in peripheral lung samples from patients with COPD. Over-expression of a miR-34a mimic caused a significant reduction in both mRNA and protein of SIRT1/-6, whereas inhibition of miR-34a (antagomir) increased these sirtuins. Induction of miR-34a expression with H2O2 was phosphoinositide-3-kinase (PI3K) dependent as it was associated with PI3Kα activation as well as phosphatase and tensin homolog (PTEN) reduction. Importantly, miR-34a antagomirs increased SIRT1/-6 mRNA levels, whilst decreasing markers of cellular senescence in airway epithelial cells from COPD patients, suggesting that this process is reversible. Other sirtuin isoforms were not affected by miR-34a. Our data indicate that miR-34a is induced by oxidative stress via PI3K signaling, and orchestrates ageing responses under oxidative stress, therefore highlighting miR-34a as a new therapeutic target and biomarker in COPD and other oxidative stress-driven aging diseases.
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影响因子：
4.1
作者：
Froejdoe, Sara;Durand, Christine;Pirola, Luciano
通讯作者：
Pirola, Luciano
影响因子：
13.5
作者：
Edwards MR;Bartlett NW;Clarke D;Birrell M;Belvisi M;Johnston SL
通讯作者：
Johnston SL
DOI：
10.1006/bbrc.2000.3000
发表时间：
2000-07-05
影响因子：
3.1
作者：
Frye, RA
通讯作者：
Frye, RA
DOI：
10.1164/rccm.201010-1605oc
发表时间：
2011-10-01
影响因子：
24.7
作者：
Kirkham, Paul A.;Caramori, Gaetano;Adcock, Ian M.
通讯作者：
Adcock, Ian M.
影响因子：
5.7
作者：
Barnes, Peter J.
通讯作者：
Barnes, Peter J.