Let-7e modulates the inflammatory response in vascular endothelial cells through ceRNA crosstalk

作者

Lin, ZW;Ge, JF;Wang, Z;Ren, JW;Wang, XW;Xiong, H;Gao, J;Zhang, Y;Zhang, QY

作者单位

[Lin, Zongwei; Wang, Xiaowei; Gao, Jing; Zhang, Qunye] Chinese Minist Educ, Key Lab Cardiovasc Remodeling & Funct Res, Jinan, Peoples R China.;-;[Lin, Zongwei; Wang, Xiaowei; Gao, Jing; Zhang, Qunye] Minist Publ Hlth, Jinan, Peoples R China.;-;[Lin, Zongwei; Wang, Xiaowei; Gao, Jing; Zhang, Qunye] State & Shandong Prov Joint Key Lab Translat Card, Jinan, Peoples R China.;-;[Lin, Zongwei; Wang, Xiaowei; Gao, Jing; Zhang, Qunye] Shandong Univ, Qilu Hosp, Jinan, Peoples R China.;-;[Ge, Junfeng] Second Peoples Hosp Jinan, Jinan, Peoples R China.;-;[Wang, Zhe] Shandong Univ, Shandong Prov Hosp, Div Endocrinol & Metab, Jinan, Peoples R China.;-;[Ren, Jianwei] Gen Staff Dept Chinese PLA, Hlth Div Guard Bur, Beijing, Peoples R China.;-;[Xiong, Hui] Shandong Univ, Shandong Acad Med Sci, Shandong Canc Hosp, Jinan, Peoples R China.;-;[Zhang, Yan] Shandong Univ, Dept Pharmacol, Sch Med, Jinan, Peoples R China.

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.

关键词

LONG NONCODING RNA; COMPETING ENDOGENOUS RNA; KAPPA-B PATHWAY; MICRORNA LET-7E; IN-VITRO; OX-LDL; EXPRESSION; DYSFUNCTION; BETA; DIFFERENTIATION

基本信息

所属机构:

归属医师: 王哲

PMID：28195197

UT：000393942900001

刊名:SCIENTIFIC REPORTS

年，卷(期):2017年7卷

DOI：10.1038/srep42498

附件： pdf

收录: SCIE