title: Let-7e modulates the inflammatory response in vascular endothelial cells through ceRNA crosstalk.
abstract: 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.
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Ministry of Public Health; The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine; Qilu Hospital, Shandong University, Jinan, China.
authors.forename: Zongwei
authors.initials: Z
authors.lastname: Lin
authors.affiliation: The Second People's Hospital of Jinan, Jinan, China.
authors.forename: Junfeng
authors.initials: J
authors.lastname: Ge
authors.affiliation: Division of Endocrinology and Metabolism, Shandong Provincial Hospital affiliated to Shandong University, Jinan, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Health Division of Guard Bureau, General Staff Department of Chinese PLA, Beijing, China.
authors.forename: Jianwei
authors.initials: J
authors.lastname: Ren
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Ministry of Public Health; The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine; Qilu Hospital, Shandong University, Jinan, China.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Wang
authors.affiliation: Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Sciences, Jinan, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Xiong
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Ministry of Public Health; The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine; Qilu Hospital, Shandong University, Jinan, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Gao
authors.affiliation: Department of Pharmacology, Shandong University School of Medicine, Jinan, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Ministry of Public Health; The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine; Qilu Hospital, Shandong University, Jinan, China.
authors.forename: Qunye
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D015815:Cell Adhesion Molecules / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism*; D004843:Epistasis, Genetic; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism / Q000494:pharmacology; D035683:MicroRNAs / Q000737:chemistry / Q000235:genetics*; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism; D009690:Nucleic Acid Conformation; D058226:Plaque, Atherosclerotic / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D021381:Protein Transport; D012313:RNA / Q000737:chemistry / Q000235:genetics*; D034622:RNA Interference; D062085:RNA, Long Noncoding / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics
chemical_list: D015815:Cell Adhesion Molecules; D016207:Cytokines; D008077:Lipoproteins, LDL; D035683:MicroRNAs; D016328:NF-kappa B; D062085:RNA, Long Noncoding; D012333:RNA, Messenger; C487931:mirnlet7 microRNA, human; C099252:oxidized low density lipoprotein; D012313:RNA