MiR-337-3p lowers serum LDL-C level through targeting PCSK9 in hyperlipidemic mice
文献类型：期刊论文
| 作者 | Xu, Xiaoding1,2; Dong, Yunxia1,2; Ma, Ningning1,2,3; Kong, Weiwen1,2; Yu, Chuwei1,2; Gong, Likun1,2 ; Chen, Jing1,2; Ren, Jin1,2
|
| 刊名 | METABOLISM-CLINICAL AND EXPERIMENTAL
 |
| 出版日期 | 2021-06-01 |
| 卷号 | 119页码:12 |
| 关键词 | miR-337-3p PCSK9 LDL-C Hyperlipidemia Dual regulation |
| ISSN号 | 0026-0495 |
| DOI | 10.1016/j.metabol.2021.154768 |
| 通讯作者 | Chen, Jing(jingchen@simm.ac.cn) ; Ren, Jin(jren@cdser.simm.ac.cu) |
| 英文摘要 | 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. |
| WOS关键词 | POSTTRANSCRIPTIONAL REGULATION ; MICRORNA THERAPEUTICS ; BREAST-CANCER ; HIGH-RISK ; PROLIFERATION ; SUPPRESSES ; EXPRESSION ; IDENTIFY ; INVASION ; BIOLOGY |
| 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] |
| WOS研究方向 | Endocrinology & Metabolism |
| 语种 | 英语 |
| WOS记录号 | WOS:000649316500005 |
| 出版者 | W B SAUNDERS CO-ELSEVIER INC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/297227]  |
| 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, 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,2021,119:12. |
| 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,119,12. |
| 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):12. |
入库方式： OAI收割
来源：上海药物研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。