MiR-221/222 and application of its inhibitor in preparation of drugs to regulate liver fat deposition, liver fibrosis and liver cell carcinoma

A technology of mir-221 and mir-222, applied in the field of biology, can solve the problems of target gene translation inhibition and/or messenger stability decline

Active Publication Date: 2019-01-04
RUIJIN HOSPITAL AFFILIATED TO SHANGHAI JIAO TONG UNIV SCHOOL OF MEDICINE +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0002] MicroRNAs (microRNA, miRNA) are small non-coding RNAs (usually 21–23 nucleotides in length) that bind to the 3' untranslated Regions that cause translational repression of target genes and / or decreased messenger stability

Method used

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  • MiR-221/222 and application of its inhibitor in preparation of drugs to regulate liver fat deposition, liver fibrosis and liver cell carcinoma
  • MiR-221/222 and application of its inhibitor in preparation of drugs to regulate liver fat deposition, liver fibrosis and liver cell carcinoma
  • MiR-221/222 and application of its inhibitor in preparation of drugs to regulate liver fat deposition, liver fibrosis and liver cell carcinoma

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0387] Example 1: Expression of microRNA in liver tissue

[0388] To identify microRNAs involved in hepatic lipid metabolism, inflammatory infiltration, and fibrosis formation, liver tissues were screened for microRNA expression. Analyzes were performed to identify dysregulated microRNAs in the livers of MCD-diet mice, CCl4-treated mice, and high-fat diet-induced obese C57Bl6 / J mice, all three of which are animal models of steatohepatitis. Discovered a pair of conserved and widely expressed microRNAs miR-221 and miR-222 (see figure 1 ) was upregulated in the livers of these models. q-PCR results showed that miR-221 and miR-222 were up-regulated by 2-3 times in the liver of MCD-diet mice, and miR-221 and miR-222 were up-regulated by 1 in the liver of high-fat diet-induced obese mice. -2 times (see Table 4).

[0389] Table 4: miR-221 and miR-222 are upregulated in the liver of MCD-diet mice and high-fat diet-induced obese mice.

[0390]

control diet

MCD diet...

Embodiment 2

[0394] Example 2: Knockout of miR-221 and miR-222 alleviates liver fat accumulation, inflammatory infiltration and collagen deposition, and fibrosis formation in animals

[0395] MCD diet mice are commonly used as a model of steatohepatitis. Therefore, an MCD diet model was established in control mice and miR-221 / 222 knockout mice to evaluate the effect of miR-221 / 222 on steatohepatitis. Evaluation of the knockout effect of miR-221 / 222 in the liver of KO mice (see Table 6).

[0396] Table 6: Expression levels of miR-221 and miR-222 in the liver of control mice and miR-221 / 222-LKO mice

[0397]

control mice

miR-221 / 222-LKO mice

Relative expression value of miR-221

1

0.15

Relative expression value of miR-222

1

0.11

[0398] Knockout of miR-221 and miR-222 reduces hepatic fat deposition in MCD-fed mice ( image 3 ). miR-221 / 222-LKO mice were given MCD diet for 6 weeks, and oil red stained oil red area of ​​liver sections was ...

Embodiment 3

[0418] Example 3: Overexpression of miR-221 / 222 worsens steatohepatitis caused by MCD diet, aggravates liver fat accumulation, inflammatory infiltration and collagen deposition, and fibrosis formation

[0419] Adenovirus AD-miR-221 / 222 infected the liver of miR-221 / 222LKO mice to re-express miR-221 / 222 in the liver. Using adenovirus AD-miR-221 / 222 overexpressing miR-221 / 222 and control adenovirus AD-GFP (titer 1*10 11 ) into the tail vein (200 microliters / only) of miR-221 / 222LKO mice aged 8 weeks and fed with MCD diet for 6 weeks. After 6 weeks, the expression of miR-221 / 222 in liver tissue of mice was detected, and it was found that AD-miR-221 / 222 could increase the expression of miR-221 / 222 in the liver of knockout mice (Table 15).

[0420] Table 15: miR-221 / 222 LKO mice were injected with AD-miR-221 / 222 and AD-GFP into the tail vein and fed with MCD diet for 6 weeks, the expression of miR-221 / 222 in liver tissue

[0421]

[0422] Infection of miR-221 / 222LKO mice with a...

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Abstract

The invention discloses miR-221/222 and application of its inhibitor in preparation of drugs and detection targets to regulate liver fat deposition, liver fibrosis and liver cell carcinoma; by inhibiting activity of miR-221 and/or miR-222, liver fat infiltration level, liver collagen fiber deposition, plasma cholesterol and serum transaminase are lowered, insulin resistance is improved, and malignant proliferation of liver cells is inhibited.

Description

technical field [0001] The invention belongs to the technical field of biology, and in particular relates to the preparation of miR-221 / 222 and its inhibitors for regulating hepatic fat deposition, liver fibrosis and hepatocellular carcinoma. Background technique [0002] MicroRNAs (microRNA, miRNA) are small non-coding RNAs (usually 21–23 nucleotides in length) that cause translational repression of target genes and / or decrease messenger stability by binding to the 3′ untranslated region of specific genes. The number of microRNAs discovered so far exceeds 2500, and new candidate microRNA genes are still being discovered, and their expression patterns are often developmental and / or tissue-specific, although some microRNAs are stably expressed throughout the organism. miRNA is an important gene regulator, involved in the regulation of various basic processes of the body, such as cell proliferation and apoptosis, differentiation, development, organogenesis, differentiation, sh...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12N15/113C12N15/11C12Q1/6886C12Q1/6883A61K31/7115A61K31/712A61K31/7125A61P1/16A61P35/00
CPCA61P1/16A61P35/00A61K31/7115A61K31/712A61K31/7125C12N15/113C12Q1/6883C12Q1/6886C12N2310/141A61K45/00A61P3/10A61P3/00A61P3/04A61P3/06
Inventor 宁光曹亚南姜秀丽山爱景
Owner RUIJIN HOSPITAL AFFILIATED TO SHANGHAI JIAO TONG UNIV SCHOOL OF MEDICINE
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