Let-7e modulates the inflammatory response in vascular endothelial cells through ceRNA crosstalk.
Let-7e modulates the inflammatory response in vascular endothelial cells through ceRNA crosstalk.
复制标题
Let-7e通过ceRNA串扰调节血管内皮细胞的炎症反应
DOI：
10.1038/srep42498
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发表时间：
2017-02-14
影响因子：
4.6
通讯作者：
Zhang Q
中科院分区：
文献类型：
--
作者：
Lin Z;Ge J;Wang Z;Ren J;Wang X;Xiong H;Gao J;Zhang Y;Zhang Q
血管内皮细胞（VECs）的炎症反应在许多心脑血管疾病的发生发展中起着关键作用。Let-7 e是内皮功能和炎症的重要调节剂。然而，let-7 e对血管内皮细胞炎症的影响和机制直到最近才被研究。因此，我们研究了这些问题，发现除了增殖、凋亡和细胞粘附外，let-7 e还通过复杂的网络参与炎症反应的调节，包括IκBβ和lncRNA lnc-MKI 67 IP-3。Let-7 e通过抑制NF-κB的靶基因IκBβ的表达，促进NF-κB的活化和核转位，进而增加炎症和粘附分子的表达。同时，lnc-MKI 67 IP-3作为let-7 e的海绵或竞争性内源性RNA（ceRNA），抑制其促炎作用，let-7 e降低lnc-MKI 67 IP-3表达，从而形成正反馈回路，加重炎症。此外，oxLDL处理的血管内皮细胞和动脉粥样硬化斑块中let-7 e、lnc-MKI 67 IP-3和IκBβ也异常。本研究揭示了let-7 e作为促炎介质和通过ceRNA串扰的NF-κB途径的新调控机制，包括let-7 e及其靶IκBβ和ceRNA lnc-MKI 67 IP-3。因此，该分子可能在血管内皮细胞的炎症反应和动脉粥样硬化的发展中发挥重要作用。
The inflammatory responses of vascular endothelial cells (VECs) are critical in the development of many cardio-cerebrovascular diseases. Let-7e is an important regulator of endothelial function and inflammation. However, the effects and mechanisms of let-7e on VECs inflammation have not been studied until recently. Thus, we investigated these issues and found that in addition to proliferation, apoptosis and cell adhesion, let-7e was also implicated in the regulation of inflammatory responses through a complex network, including IκBβ and lncRNA lnc-MKI67IP-3. Let-7e promoted NF-κB activation and translocation to the nucleus by inhibiting its target gene (IκBβ) expression and subsequently increased the expression of inflammatory and adhesion molecules. Meanwhile, lnc-MKI67IP-3 acted as a sponge or competing endogenous RNA (ceRNA) for let-7e, suppressing its pro-inflammatory effects, and let-7e decreased lnc-MKI67IP-3 expression, thereby forming a positive feedback loop to aggravate inflammation. Moreover, let-7e, lnc-MKI67IP-3 and IκBβ were also abnormal in oxLDL-treated VECs and atherosclerotic plaques. The present study revealed let-7e as a pro-inflammatory mediator and a novel regulatory mechanism for the NF-κB pathway through ceRNA crosstalk, comprising let-7e and its target IκBβ and the ceRNA lnc-MKI67IP-3. Thus, this molecule might play important roles in the inflammatory responses of VECs and development of atherosclerosis.