MiR-337-3p lowers serum LDL-C level through targeting PCSK9 in hyperlipidemic mice

doi:10.1016/j.metabol.2021.154768

	MiR-337-3p lowers serum LDL-C level through targeting PCSK9 in hyperlipidemic mice
	Xu, Xiaoding 1,2; Dong, Yunxia 1,2; Ma, Ningning1,2,3 ; Kong, Weiwen 1,2; Yu, Chuwei 1,2; Gong, Likun 1,2; Chen, Jing 1,2; Ren, Jin 1,2
	2021-06
发表期刊	METABOLISM-CLINICAL AND EXPERIMENTAL (IF:10.8[JCR-2023],10.6[5-Year])
ISSN	0026-0495
EISSN	1532-8600
卷号	119
DOI	10.1016/j.metabol.2021.154768
摘要	Background: Reducing serum low-density lipoprotein cholesterol (LDL-C) in hyperlipemia is recognized as an effective strategy to minimize the risk of atherosclerotic cardiovascular disease (ASCVD). MiR-337-3p has already been discovered to play regulatory roles in tumor proliferation and metastasis, adipocyte browning and ischemic brain injury, etc. However, the association between miR-337-3p and LDL-C is unknown. Methods: Gene Expression Omnibus (GEO) dataset and two hyperlipidemic murine models were used to analyze the potential relationship between miR-337-3p and LDL-C. AAV-mediated liver-directed miRNA over expression in high fat diet (HFD)-fed mouse model was used to examine the effect of miR-337-3p on LDL-C and WB/RT-PCR/ELISA/luciferase assays were used to investigate the underlying mechanism. Results: The expressions of miR-337-3p were obviously lower in multiple hyperlipidemic mouse models and had a negative correlation with serum LDL-C levels. After confirming the effect of miR-337-3p on the improvement of serum LDL-C in vivo, we discovered PCSK9 might be a possible target of miR-337-3p, which was further proved by in vitro experiments. MiR-337-3p could directly interact with both the PCSK9 3 ' UTR and promoter to inhibit PCSK9 translation and transcription. Furthermore, the result from DiI-LDL uptake assay under the knockdown of PCSK9 demonstrated that miR-337-3p promoting the absorption of LDL-C in HepG2 cells was dependent on PCSK9, and the result from LDLR & minus;/& minus; mouse model indicated that miR-337-3p regulating LDL-C was dependent on PCSK9/LDLR pathway. Conclusion: We discovered a new function of miR-337-3p in regulating PCSK9 expression and LDL-C absorption, suggesting miR-337-3p might be a new therapeutic target for the development of antihyperlipidemic drug. (c) 2021 Elsevier Inc. All rights reserved.
关键词	miR-337-3p PCSK9 LDL-C Hyperlipidemia Dual regulation
收录类别	SCIE
语种	英语
WOS研究方向	Endocrinology & Metabolism
WOS类目	Endocrinology & Metabolism
WOS记录号	WOS:000649316500005
出版者	W B SAUNDERS CO-ELSEVIER INC
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/126791
专题	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, Shanghai Inst Mat Med, State Key Lab Drug Res, Ctr Drug Safety Evaluat & Res, 501 Haike Rd, Shanghai 201203, Peoples R China; 2.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China; 3.ShanghaiTech Univ, Sch Life Sci & Technol, 100 Haike Rd, Shanghai 201210, Peoples R China
推荐引用方式 GB/T 7714	Xu, Xiaoding,Dong, Yunxia,Ma, Ningning,et al. MiR-337-3p lowers serum LDL-C level through targeting PCSK9 in hyperlipidemic mice[J]. METABOLISM-CLINICAL AND EXPERIMENTAL,2021,119.
APA	Xu, Xiaoding.,Dong, Yunxia.,Ma, Ningning.,Kong, Weiwen.,Yu, Chuwei.,...&Ren, Jin.(2021).MiR-337-3p lowers serum LDL-C level through targeting PCSK9 in hyperlipidemic mice.METABOLISM-CLINICAL AND EXPERIMENTAL,119.
MLA	Xu, Xiaoding,et al."MiR-337-3p lowers serum LDL-C level through targeting PCSK9 in hyperlipidemic mice".METABOLISM-CLINICAL AND EXPERIMENTAL 119(2021).