Over-expression of microRNA-494 up-regulates hypoxia-inducible factor-1 alpha expression via PI3K/Akt pathway and protects against hypoxia-induced apoptosis.
Over-expression of microRNA-494 up-regulates hypoxia-inducible factor-1 alpha expression via PI3K/Akt pathway and protects against hypoxia-induced apoptosis.
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microRNA-494 的过表达通过 PI3K/Akt 途径上调缺氧诱导因子 1 α 表达，并防止缺氧诱导的细胞凋亡
DOI：
10.1186/1423-0127-20-100
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发表时间：
2013-12-23
影响因子：
11
通讯作者：
Feng L
中科院分区：
文献类型：
--
作者：
Sun G;Zhou Y;Li H;Guo Y;Shan J;Xia M;Li Y;Li S;Long D;Feng L
缺氧诱导因子-1 α（Hypoxia-inducible factor-1 alpha，HIF-1α）是缺氧/缺血的关键调节因子之一。microRNA-494（miR-494）对缺血/再灌注（I/R）诱导的心肌损伤具有保护作用，但其与HIF-1α的功能关系尚不清楚。本研究旨在确定miR-494是否参与HIF-1α的诱导。定量RT-PCR结果显示，人肝细胞株L02在缺氧4 h后，miR-494表达上调至峰值。为了研究miR-494的作用，用miR-494模拟物或miR阴性对照转染细胞，然后在常氧或缺氧下孵育。结果表明，与阴性对照组相比，过表达miR-494可显著诱导p-Akt、HIF-1α和HO-1在常氧和缺氧条件下的表达（p <0. 05）。LY 294002处理显著消除了miR-494诱导的Akt活化，但在常氧和缺氧条件下HIF-1α和HO-1均增加（p < 0.05）。此外，使用Annexin V的凋亡检测表明，与对照相比，miR-494的过表达显著降低了L02细胞中缺氧诱导的凋亡（p < 0.05）。在缺氧条件下，MiR-494过表达还使L02细胞中caspase-3/7活性降低了1.27倍。过表达miR-494可通过激活PI 3 K/Akt信号通路上调常氧和缺氧条件下L02细胞HIF-1α的表达，对缺氧诱导的细胞凋亡具有保护作用。因此，这些发现表明miR-494可能是治疗肝缺氧/缺血损伤的靶点。
Hypoxia-inducible factor-1 alpha (HIF-1α) is one of the key regulators of hypoxia/ischemia. MicroRNA-494 (miR-494) had cardioprotective effects against ischemia/reperfusion (I/R)-induced injury, but its functional relationship with HIF-1α was unknown. This study was undertaken to determine if miR-494 was involved in the induction of HIF-1α. Quantitative RT-PCR showed that miR-494 was up-regulated to peak after 4 hours of hypoxia in human liver cell line L02. To investigate the role of miR-494, cells were transfected with miR-494 mimic or miR-negative control, followed by incubation under normoxia or hypoxia. Our results indicated that overexpression of miR-494 significantly induced the expression of p-Akt, HIF-1α and HO-1 determined by qRT-PCR and western blot under normoxia and hypoxia, compared to negative control (p < 0.05). While LY294002 treatment markedly abolished miR-494-inducing Akt activation, HIF-1α and HO-1 increase under both normoxic and hypoxic conditions (p < 0.05). Moreover, apoptosis detection using Annexin V indicated that overexpression of miR-494 significantly decreased hypoxia-induced apoptosis in L02 cells, compared to control (p < 0.05). MiR-494 overexpression also decreased caspase-3/7 activity by 1.27-fold under hypoxia in L02 cells. Overexpression of miR-494 upregulated HIF-1α expression through activating PI3K/Akt pathway under both normoxia and hypoxia, and had protective effects against hypoxia-induced apoptosis in L02 cells. Thus, these findings suggested that miR-494 might be a target of therapy for hepatic hypoxia/ischemia injury.
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影响因子：
20.1
作者：
Rane S;He M;Sayed D;Vashistha H;Malhotra A;Sadoshima J;Vatner DE;Vatner SF;Abdellatif M
通讯作者：
Abdellatif M
DOI：
10.4161/cc.9.6.11006
发表时间：
2010-03-15
期刊：
Cell cycle (Georgetown, Tex.)
影响因子：
--
作者：
Chan SY;Loscalzo J
通讯作者：
Loscalzo J
影响因子：
--
作者：
Adams, J. M.;Difazio, L. T.;Nemeth, Z. H.
通讯作者：
Nemeth, Z. H.
影响因子：
11.2
作者：
Taguchi, Ayumu;Yanagisawa, Kiyoshi;Takahashi, Takashi
通讯作者：
Takahashi, Takashi
DOI：
10.1165/rcmb.2012-0430oc
发表时间：
2013-10-01
影响因子：
6.4
作者：
Ramachandran, Shyam;Karp, Philip H.;McCray, Paul B., Jr.
通讯作者：
McCray, Paul B., Jr.