New PCSK9 inhibitor miR-552-3p reduces LDL-C via enhancing LDLR in high fat diet-fed mice

doi:10.1016/j.phrs.2021.105562

	New PCSK9 inhibitor miR-552-3p reduces LDL-C via enhancing LDLR in high fat diet-fed mice
	Ma, Ningning1,2,3 ; Fan, Lei 1,3; Dong, Yunxia 1,3; Xu, Xiaoding 1,3; Yu, Chuwei 1,3; Chen, Jing 1,3; Ren, Jin1,2,3
	2021-05
发表期刊	PHARMACOLOGICAL RESEARCH (IF:9.1[JCR-2023],9.0[5-Year])
ISSN	1043-6618
EISSN	1096-1186
卷号	167
DOI	10.1016/j.phrs.2021.105562
摘要	PCSK9 has emerged as a promising new therapeutic target for hyperlipidemia. The efficacy of PCSK9 siRNA in clinic trials clues the feasibility of exploring more PCSK9 inhibitors based on genetic inhibition in the treatment of hyperlipidemia. MicroRNAs (miRNAs) as a class of endogenous non-coding small RNAs can regulate genes at transcriptional and/or translational level. Here, we screened miRNAs from the prediction of TargetScan database with possible inhibitory activities in PCSK9 protein level via AlphaLISA and Western blotting, in which miR-5523p was selected out for its strongest inhibitory effect. MiR-552-3p could bind to the 3' untranslated region (3'UTR) of PCSK9 to inhibit translation and interact with the promoter of PCSK9 to suppress transcription. Further in vitro and in vivo experiments proved the effects of miR-552-3p on PCSK9 and downstream effectors: it could increase LDLR protein level, promote LDL-C uptake in HepG2 cells and lower serum LDL-C in high fat diet (HFD)fed mice. In conclusion, our findings firstly identified miR-552-3p as a new PCSK9 inhibitor with the dualinhibition mechanism, which suggested the possible application of miR-552-3p in the treatment of hyperlipidemia.
关键词	PCSK9 Hyperlipidemia MiR-552-3p 3 '-UTR Promoter
收录类别	SCIE
语种	英语
WOS研究方向	Pharmacology & Pharmacy
WOS类目	Pharmacology & Pharmacy
WOS记录号	WOS:000643618900035
出版者	ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
原始文献类型	Article
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/126950
专题	生命科学与技术学院_特聘教授组_任进组生命科学与技术学院_博士生
通讯作者	Chen, Jing; Ren, Jin
作者单位	1.Chinese Acad Sci, Ctr Drug Safety Evaluat & Res, Shanghai Inst Mat Med, State Key Lab Drug Res, 501 Haike Rd, Shanghai 201203, Peoples R China; 2.Shanghai Tech Univ, Sch Life Sci & Technol, 100 Haike Rd, Shanghai 201210, Peoples R China; 3.Univ Chinese Acad Sci, 19 A Yuquan Rd, Beijing 100049, Peoples R China
第一作者单位	生命科学与技术学院
通讯作者单位	生命科学与技术学院
推荐引用方式 GB/T 7714	Ma, Ningning,Fan, Lei,Dong, Yunxia,et al. New PCSK9 inhibitor miR-552-3p reduces LDL-C via enhancing LDLR in high fat diet-fed mice[J]. PHARMACOLOGICAL RESEARCH,2021,167.
APA	Ma, Ningning.,Fan, Lei.,Dong, Yunxia.,Xu, Xiaoding.,Yu, Chuwei.,...&Ren, Jin.(2021).New PCSK9 inhibitor miR-552-3p reduces LDL-C via enhancing LDLR in high fat diet-fed mice.PHARMACOLOGICAL RESEARCH,167.
MLA	Ma, Ningning,et al."New PCSK9 inhibitor miR-552-3p reduces LDL-C via enhancing LDLR in high fat diet-fed mice".PHARMACOLOGICAL RESEARCH 167(2021).