Overexpression of circRNA circUCK2 Attenuates Cell Apoptosis in Cerebral Ischemia-Reperfusion Injury via miR-125b-5p/GDF11 Signaling.
Overexpression of circRNA circUCK2 Attenuates Cell Apoptosis in Cerebral Ischemia-Reperfusion Injury via miR-125b-5p/GDF11 Signaling.
复制标题
circRNA circUCK2 过表达通过 miR-125b-5p/GDF11 信号减弱脑缺血再灌注损伤中的细胞凋亡
DOI：
10.1016/j.omtn.2020.09.032
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发表时间：
2020-12-04
期刊：
影响因子：
--
通讯作者：
Chen L
中科院分区：
文献类型：
--
作者：
Chen W;Wang H;Feng J;Chen L
环状RNA（circRNA）在大脑中以高水平表达，并且参与各种中枢神经系统疾病。然而，circRNA在缺血性卒中相关神经元损伤中的潜在作用在很大程度上仍然未知。本研究旨在揭示circRNA UCK 2（circUCK 2）在缺血性脑卒中中的作用及其机制。采用HT-22细胞氧糖剥夺模型模拟缺血性脑卒中。分别用细胞计数试剂盒-8（CCK-8）和TUNEL（末端脱氧核苷酸转移酶介导的脱氧尿苷三磷酸缺口末端标记）染色法测定神经元活力和凋亡。采用小鼠大脑中动脉闭塞法检测circUCK 2的功能。在小鼠局灶性脑缺血再灌注模型的脑组织中，circUCK 2的水平显著降低。上调的circUCK 2水平显著降低梗死体积，减轻神经元损伤，并改善神经功能缺损。circUCK 2通过调节转化生长因子β（TGF-β）/mothers对抗十肢瘫痪同源物3（Smad 3）信号转导来减少氧葡萄糖剥夺（OGD）诱导的细胞凋亡。此外，circUCK 2作为内源性miR-125 b-5 p海绵发挥作用，抑制miR-125 b-5 p活性，导致生长分化因子11（GDF 11）表达增加，随后改善神经元损伤。因此，这些发现表明circUCK 2/miR-125 b-5 p/GDF 11轴是缺血性卒中期间的重要信号传导途径。因此，circRNA circUCK 2可能作为缺血性卒中患者新治疗的潜在靶点。Chen及其同事发现，过表达的circRNA UCK 2（circUCK 2）通过调节TGF-β/Smad 3信号转导来减轻缺血性神经元损伤。此外，circUCK 2作为内源性miR-125 b-5 p海绵发挥作用，抑制miR-125 b-5 p活性，导致GDF 11表达增加，随后改善神经元损伤。
Circular RNAs (circRNAs) are expressed at high levels in the brain and are involved in various central nervous system diseases. However, the potential role of circRNAs in ischemic stroke-associated neuronal injury remains largely unknown. Herein, we uncovered the function and underlying mechanism of the circRNA UCK2 (circUCK2) in ischemia stroke. The oxygen-glucose deprivation model in HT-22 cells was used to mimic ischemia stroke in vitro. Neuronal viability and apoptosis were determined by Cell Counting Kit-8 (CCK-8) assays and TUNEL (terminal deoxynucleotidyltransferase-mediated deoxyuridine triphosphate nick end labeling) staining, respectively. Middle cerebral artery occlusion was conducted to evaluate the function of circUCK2 in mice. The levels of circUCK2 were significantly decreased in brain tissues from a mouse model of focal cerebral ischemia and reperfusion. Upregulated circUCK2 levels significantly decreased infarct volumes, attenuated neuronal injury, and improved neurological deficits. circUCK2 reduced oxygen glucose deprivation (OGD)-induced cell apoptosis by regulating transforming growth factor β (TGF-β)/mothers against decapentaplegic homolog 3 (Smad3) signaling. Furthermore, circUCK2 functioned as an endogenous miR-125b-5p sponge to inhibit miR-125b-5p activity, resulting in an increase in growth differentiation factor 11 (GDF11) expression and a subsequent amelioration of neuronal injury. Consequently, these findings showed that the circUCK2/miR-125b-5p/GDF11 axis is an essential signaling pathway during ischemia stroke. Thus, the circRNA circUCK2 may serve as a potential target for novel treatment in patients with ischemic stroke. Chen and colleagues found that overexpressed circRNA UCK2 (circUCK2) attenuated ischemic neuronal injury by regulating TGF-β/Smad3 signaling. Furthermore, circUCK2 functioned as an endogenous miR-125b-5p sponge to inhibit miR-125b-5p activity, resulting in an increase in GDF11 expression and a subsequent amelioration of neuronal injury.
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影响因子：
6.1
作者：
Gao BY;Sun CC;Xia GH;Zhou ST;Zhang Y;Mao YR;Liu PL;Zheng Y;Zhao D;Li XT;Xu J;Xu DS;Bai YL
通讯作者：
Bai YL
影响因子：
17.1
作者：
Cheng, Rui;Huang, Weijie;Huang, Lijie;Yang, Bo;Mao, Leidong;Jin, Kunlin;ZhuGe, Qichuan;Zhao, Yiping
通讯作者：
Zhao, Yiping
影响因子：
12.4
作者：
Jin, Quan;Qiao, Chunping;Xiao, Xiao
通讯作者：
Xiao, Xiao
影响因子：
5.4
作者：
Che, Fengli;Du, Huishan;Tong, Yanna
通讯作者：
Tong, Yanna
影响因子：
5.2
作者：
Hudobenko, Jacob;Ganesh, Bhanu Priya;Chauhan, Anjali
通讯作者：
Chauhan, Anjali