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

文献类型：期刊论文

作者Ma, Ningning1,2,3; Fan, Lei1,3; Dong, Yunxia1,3; Xu, Xiaoding1,3; Yu, Chuwei1,3; Chen, Jing1,3; Ren, Jin1,2,3
刊名PHARMACOLOGICAL RESEARCH
出版日期2021-05-01
卷号167页码:13
关键词PCSK9 Hyperlipidemia MiR-552-3p 3 '-UTR Promoter
ISSN号1043-6618
DOI10.1016/j.phrs.2021.105562
通讯作者Chen, Jing(jingchen@simm.ac.cn) ; Ren, Jin(jren@cdser.simm.ac.cn)
英文摘要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.
WOS关键词CANCER ; MIRNA ; EXPRESSION ; TRANSCRIPTION ; THERAPEUTICS ; BIOGENESIS ; INCLISIRAN ; DELIVERY ; BINDING ; DRUG
资助项目National Natural Science Foundation of China[81870401] ; National Science & Technology Major Project Key New Drug Creation and Manufacturing Program, China[2018ZX09101001-003-007] ; Novo Nordisk-Chinese Academy of Sciences (NN-CAS) Research Fund[NNCAS-2017-21-JRP]
WOS研究方向Pharmacology & Pharmacy
语种英语
WOS记录号WOS:000643618900035
出版者ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
源URL[http://119.78.100.183/handle/2S10ELR8/297263]  
专题新药研究国家重点实验室
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
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,2021,167:13.
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,167,13.
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):13.

入库方式： OAI收割

来源：上海药物研究所

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