标题：Let-7e modulates the inflammatory response in vascular endothelial cells through ceRNA crosstalk
作者：Lin, Zongwei; Ge, Junfeng; Wang, Zhe; Ren, Jianwei; Wang, Xiaowei; Xiong, Hui; Gao, Jing; Zhang, Yan; Zhang, Qunye
作者机构：[Lin, Zongwei; Wang, Xiaowei; Gao, Jing; Zhang, Qunye] Chinese Minist Educ, Key Lab Cardiovasc Remodeling & Funct Res, Jinan, Peoples R China.; [Lin 更多
通讯作者：Zhang, QY;Zhang, QY;Zhang, QY;Zhang, QY;Zhang, Y
通讯作者地址：[Zhang, QY]Chinese Minist Educ, Key Lab Cardiovasc Remodeling & Funct Res, Jinan, Peoples R China;[Zhang, QY]Minist Publ Hlth, Jinan, Peoples R China; 更多
摘要：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 I kappa B beta and lncRNA lnc-MKI67IP-3. Let-7e promoted NF-kappa B activation and translocation to the nucleus by inhibiting its target gene (I kappa B beta) 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 I kappa B beta 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-kappa B pathway through ceRNA crosstalk, comprising let-7e and its target I kappa B beta and the ceRNA lnc-MKI67IP-3. Thus, this molecule might play important roles in the inflammatory responses of VECs and development of atherosclerosis.