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Application of microRNA or inhibitor thereof to lipid metabolism regulation

A technology of inhibitors and lipid metabolism, applied in the direction of DNA / RNA fragments, metabolic diseases, recombinant DNA technology, etc., can solve the problem of macrophages' ability to absorb lipoproteins, etc.

Active Publication Date: 2014-08-06
MEDICINE & BIOENG INST OF CHINESE ACAD OF MEDICAL SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Studies have shown that PPAR-γ may inhibit the expression of scavenger receptor SR-A (scavenger receptor A) by inhibiting the activity of transcription factor activation protein-1 (AP-1), leading to the uptake of lipids by macrophages. Decreased protein capacity

Method used

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  • Application of microRNA or inhibitor thereof to lipid metabolism regulation
  • Application of microRNA or inhibitor thereof to lipid metabolism regulation
  • Application of microRNA or inhibitor thereof to lipid metabolism regulation

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0113] Example 1, miR-96, miR-185 and miR-223 regulate SR-BI, an important target of cholesterol reverse transport.

[0114] 1.1. Effect of Dicer and Drosha gene silencing on SR-BI mRNA level

[0115] After knocking out two key enzymes Dicer and Drosha in the process of microRNA biosynthesis by siRNA gene silencing technology, the Real-time RT-PCR method was used to detect the level of SR-BI mRNA.

[0116] The experimental results showed that after Dicer or Drosha gene silencing, the level of SR-BI mRNA was significantly up-regulated, indicating that microRNA is involved in the regulation of SR-BI (such as figure 1shown).

[0117] 1.2. Regulatory effects of miR-96, miR-185, miR-223 and their antagonists on SR-BI mRNA and protein expression levels.

[0118] The miRNA antagonist (anti-miR) of the present invention is purchased from QIAGEN, and its sequence and article number are respectively:

[0119] anti-miR-96 (Cat.no.MIN0000095)

[0120] 5'-agcaaaaaugugcuagugccaaa-3' (...

Embodiment 2

[0140] Example 2, the regulation of miR-96 and miR-223 on ABCA1, an important target of cholesterol reverse transport.

[0141] 2.1. Target prediction and homology analysis of miR-96, miR-223 and ABCA13'UTR.

[0142] MicroRNA.org and TargetScan predicted the interaction sites of miR-96 and miR-223 with ABCA13'UTR. The predicted target sequences of miR-96 and miR-223 of ABCA13'UTR of multiple species were compared using Clustal X2 software.

[0143] Forecast results such as Figure 8 As shown, there is one predicted target of miR-96 and one of miR-223 on ABCA13'UTR. The sequence alignment results are as Figure 9 As shown, the predicted targets of miR-96 and miR-223 present on ABCA13'UTR showed sequence conservation in multiple species (Hsa human; Ptr chimpanzee; Pab Sumatran chimpanzee; Ame giant panda; Mmu mouse).

[0144] 2.2 Regulatory effects of miR-96, miR-223 and their antagonists on ABCA1 mRNA levels

[0145] Lipofectamine RNAiMAX Transfection Reagent transiently...

Embodiment 3

[0147] Example 3, regulation of LDLR by miR-185 and its antagonists.

[0148] 3.1. Prediction and homology analysis of direct action targets of miR-185 and LDLR3'UTR.

[0149] MicroRNA.org and TargetScan predicted the interaction sites of miR-185 and LDLR3'UTR. Clustal X2 software was used to compare the miR-185 predicted target sequences of LDLR3'UTR in multiple species.

[0150] Forecast results such as Figure 11 As shown, there are two predicted targets of miR-185 on LDLR3'UTR. The sequence alignment results are as Figure 12 As shown, the predicted target of miR-185 present on LDLR3'UTR exhibits sequence conservation in multiple species (Hsa human; Ptr chimpanzee; Pab Sumatran chimpanzee; Bta cattle).

[0151] 3.2. Regulation of LDLR mRNA levels by miR-185 and its antagonists

[0152]Lipofectamine RNAiMAX Transfection Reagent was used to transiently transfect miR-185 or its antisense oligonucleotide inhibitor into liver cancer cell HepG2 cells, and after 72 hours o...

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Abstract

The invention relates to the purpose of microRNA or inhibitors thereof, and in particular to application of microRNA and inhibitors thereof to preparation of medicaments for regulating lipid metabolism or preparation of medicaments for preventing or treating diseases related to lipid metabolism. The microRNA includes one or more selected from miRNA-96, miRNA-185 and miRNA-223. The invention also relates to the application of the microRNA or inhibitors thereof for to regulation of expression level of lipid metabolism-related proteins. The invention also relates to a composition comprising the microRNA or inhibitors thereof. The microRNA or inhibitors thereof provided by the invention can be used as pharmaceutical compositions for application to prevention or treatment of hyperlipidemia, atherosclerosis and coronary heart diseases.

Description

technical field [0001] The present invention relates to the use of microRNA or its inhibitor, in particular to the use of microRNA or its inhibitor in the preparation of medicines for regulating lipid metabolism or the preparation of medicines for preventing or treating diseases related to lipid metabolism. In addition, microRNA or its inhibitors can be used as a tool drug for the above-mentioned related diseases or the functional mechanism research of related proteins. The present invention also relates to the use of the microRNA or its inhibitor for regulating the expression level of lipid metabolism-related proteins. The present invention also relates to compositions comprising said microRNA or its antisense oligonucleotide inhibitor. Background technique [0002] Atherosclerotic cardiovascular and cerebrovascular diseases are the most disabling and fatal diseases worldwide, and dyslipidemia is one of the most important risk factors for atherosclerosis. It has been a lo...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/00A61K48/00A61P3/00A61P3/06A61P9/10A61P9/00A61P25/28A61P3/04A61P3/10C12Q1/68
CPCA61K31/7105A61K31/713A61P3/00A61P3/04A61P3/06A61P3/10A61P9/00A61P9/10A61P25/28C12N15/113C12N2310/113C12N2310/141C12Q1/6883C12Q2600/136C12Q2600/158C12Q2600/178G01N2405/00G01N2500/04G01N2800/044C12N2320/30C12Q1/6897G01N33/92G01N2500/10
Inventor 洪斌王丽贾晓健姜华军杜郁杨帆司书毅
Owner MEDICINE & BIOENG INST OF CHINESE ACAD OF MEDICAL SCI
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