CN110496134A - The application of miR-153-3p and its chaff interferent and product - Google Patents
The application of miR-153-3p and its chaff interferent and product Download PDFInfo
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- CN110496134A CN110496134A CN201910903457.6A CN201910903457A CN110496134A CN 110496134 A CN110496134 A CN 110496134A CN 201910903457 A CN201910903457 A CN 201910903457A CN 110496134 A CN110496134 A CN 110496134A
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Classifications
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
- A61K31/7105—Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
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Abstract
The present invention relates to field of biotechnology, specifically, providing application and the product of a kind of miR-153-3p and its chaff interferent.Inventor has found that miR-153-3p participates in adjusting cardiac myocyte hypertrophy by forming the signal path of NFATC3/miR-153-3p/Mfn1 by influencing chondriokinesis by research for the first time.Therefore, miR-153-3p can be used as early diagnosis or the auxiliary diagnosis marker of heart disease, realizes the early diagnosis early treatment of heart disease, diagnosis or auxiliary diagnosis may be implemented for the kit of miR-153-3p detection；In addition, inventor's discovery may be implemented just to intervene early stage cardiac muscle cell occurs loose, realize that the early stage of heart disease effectively prevents or treats by inhibiting miR-153-3p.
Description
Technical field
The present invention relates to biopharmaceutical technology, in particular to answering for a kind of miR-153-3p and its chaff interferent
With with product.
Background technique
Myocardial hypertrophy is the compensatory response that cardiac muscle continues to increase cardiac load, is mainly characterized by cardiac muscle cell's body
Product/surface area increases, and cardiac weight increases, stromal cell proliferation and Myocardial Remodeling.Pathological heart hypertrophy and remodeling ventricle and
Cardiac insufficiency is related, this is as caused by many cardiovascular diseases.Myocardial hypertrophy is directed not only to cardiac muscular tissue and ventricle wall/room
The abnormal of interval increases, also with embryonic gene, the up-regulation of myocardial fibrosis and cardiac insufficiency.Mitochondria dysfunction is logical
It crosses the generation for increasing active oxygen and mitochondrial oxidation stress damage, excessive consumption ATP and mitochondria dynamics dysfunction and leads
An important factor for causing various cardiovascular diseases to develop.The dynamic (dynamical) imbalance of mitochondria, refer to abnormal chondriokinesis and
Fusion, is the correlative factor of cardiomegaly pathogenesis.
Microrna (miRNA) is the single-stranded short non-coding RNA of endogenous, inhibits protein by mediating the degradation of mRNA
Expression.MiRNA plays an important role in the Gene expression and regulation of transcription and post-transcriptional level.There is ample evidence to show that miRNA is
Cell Proliferation, the Primary Actor of the basal cells event such as Apoptosis and development.Many evidences show that miRNA is also cardiac muscle
The key regulator of cellular mast pathogenesis.Although more and more miRNA as human diseases biomarker and
Therapy target is found, but the research of the crucial miRNA in heart disease and its mechanism is also seldom, needs further to be sent out
It is existing.
In view of this, the present invention is specifically proposed.
Summary of the invention
The first object of the present invention, which is to provide, provides heart disease relevant novel targets, may be implemented to send out in cardiac muscle cell
Raw loose early stage is just intervened, which can be applied in the diagnosis and prevention and treatment of heart disease.
The second object of the present invention be to provide present invention discover that novel targets chaff interferent preparation for diagnosing, preventing
Or the application in the product for the treatment of heart disease, diagnosis, prevention or the effective means for treating heart disease are provided.
The third object of the present invention is to provide a kind of for diagnosing or the kit of auxiliary diagnosis heart disease, provides one
The new product of kind diagnosis or auxiliary diagnosis heart disease.
The fourth object of the present invention is to provide a kind of for preventing or the drug of Diagnosing Cardiac disease, provides prevention or controls
Treat the effective means of early stage cardiac disease.
In order to realize above-mentioned purpose of the invention, the following technical scheme is adopted:
1. in following (a)-(d) any substance preparation for diagnose or the product of auxiliary diagnosis heart disease in answer
With:
(a) miR-153-3p, nucleotide sequence is as shown in SEQ ID NO.1:
5'-UUGCAUAGUCACAAAAGUGAUC-3'；
(b) there is the nucleotide sequence of 70% or more homology with the nucleotide sequence of (a)；
(c) nucleotide sequence of miR-153-3p is transcribed, sequence is as shown in SEQ ID NO.8:
5'-TTGCATAGTCACAAAAGTGATC-3'；
(d) there is the nucleotide sequence of 70% or more homology with the nucleotide sequence of (c).
Further, the heart disease includes myocardial infarction, treating myocardial ischemia damage, myocardial hypertrophy, heart failure, cardiac muscle
At least one of fibrosis or cardiomyopathy.
Further, the product includes kit.
As follows in (a)-(d) chaff interferent of any substance in preparing product for preventing or treating heart disease
Using:
(a) miR-153-3p, nucleotide sequence is as shown in SEQ ID NO.1:
5'-UUGCAUAGUCACAAAAGUGAUC-3'；
(b) there is the nucleotide sequence of 70% or more homology with the nucleotide sequence of (a)；
(c) nucleotide sequence of miR-153-3p is transcribed, sequence is as shown in SEQ ID NO.8:
5'-TTGCATAGTCACAAAAGTGATC-3'；
(d) there is the nucleotide sequence of 70% or more homology with the nucleotide sequence of (c).
Further, the chaff interferent includes the GEM 132 of any substance in a)-(d)；
Preferably, the sequence of the GEM 132 of the miR-153-3p is as shown in SEQ ID NO.2；
The GEM 132 of miR-153-3p: 5 '-GAUCACUUUUGUGACUAUGCAA-3 ' (SEQ ID NO.2)；
Preferably, the GEM 132 of the miR-153-3p has chemical modification；
Preferably, the chemical modification includes that phosphoric acid backbone modification, ribose modification, base modification or lock nucleic acid are modified, into
One step is preferably ribose modification, is still more preferably the modification of each 2 ' position methoxyl group of base.
Further, the heart disease includes myocardial infarction, treating myocardial ischemia damage, myocardial hypertrophy, heart failure, cardiac muscle
At least one of fibrosis or cardiomyopathy；
Preferably, the product includes kit, drug, health care product or food.
It is a kind of for diagnosing or the kit of auxiliary diagnosis heart disease, the kit includes detection miR-153-3p
Substance, the sequence of miR-153-3p is as shown in SEQ ID NO.1；
MiR-153-3p:5 '-UUGCAUAGUCACAAAAGUGAUC-3 ' (SEQ ID NO.1).
It is a kind of for preventing or treating the product of heart disease, the product includes the chaff interferent in above-mentioned application.
Further, the product includes kit, drug, health care product or food.
Further, the drug further includes pharmaceutically acceptable carrier or auxiliary material；
Preferably, the administration mode of the drug be selected from oral, intravenous injection, intramuscular injection, intracoronary injection or
Direct myocardial injection.
Compared with prior art, the invention has the benefit that
Inventor is by studying the signal for finding miR-153-3p for the first time by forming NFATC3/miR-153-3p/Mfn1
Access participates in adjusting cardiac myocyte hypertrophy by influencing chondriokinesis.Therefore, miR-153-3p can be used as heart disease
Early diagnosis or auxiliary diagnosis marker, the early diagnosis early treatment of heart disease is realized, for the examination of miR-153-3p detection
Diagnosis or auxiliary diagnosis may be implemented in agent box；In addition, inventor's discovery may be implemented by inhibiting miR-153-3p myocardium thin
The early stage that hypertrophy occurs for born of the same parents just intervenes, and realizes that the early stage of heart disease effectively prevents or treats.So miR-153-3p and
The nucleotide sequence of transcription miR-153-3p can be applied in diagnosis or auxiliary diagnosis heart disease, and have therewith
The nucleotide sequence of 70% or more homology can also be used as novel targets application.
Detailed description of the invention
It, below will be to specific in order to illustrate more clearly of the specific embodiment of the invention or technical solution in the prior art
Embodiment or attached drawing needed to be used in the description of the prior art be briefly described, it should be apparent that, it is described below
Attached drawing is some embodiments of the present invention, for those of ordinary skill in the art, before not making the creative labor
It puts, is also possible to obtain other drawings based on these drawings.
Fig. 1 is miRNA-153-3p expression during ISO inducing cardiomyocytes are loose in embodiment 1；
Fig. 2A is the endogenous expression of results that miRNA-153-3p GEM 132 inhibits miRNA-153-3p in embodiment 2
Figure；
Fig. 2 B is that miRNA-153-3p GEM 132 influences result to the cell surface of cardiac muscle cell product in embodiment 2；
Fig. 2 C is miRNA-153-3p GEM 132 in embodiment 2 to the loose marker ANP and β-MHC of cardiac muscle cell
Influence result；
Fig. 3 A is miRNA-153-3p GEM 132 in embodiment 3 to the heart weight weight ratio shadow of ISO induced mouse model
Ring result；
Fig. 3 B is that miRNA-153-3p GEM 132 is long-pending to the cell cross section of ISO induced mouse model in embodiment 3
Influence result；
Fig. 3 C is miRNA-153-3p GEM 132 in embodiment 3 to cardiac muscle cell's ANP table of ISO induced mouse model
Result is influenced up to amount；
Fig. 3 D is miRNA-153-3p GEM 132 in embodiment 3 to the myocardial collagen content of ISO induced mouse model
Influence result；
Fig. 3 E is miRNA-153-3p GEM 132 in embodiment 3 to the cardiac ejection fraction of ISO induced mouse model
Influence result.
Specific embodiment
Embodiment of the present invention is described in detail below in conjunction with embodiment, but those skilled in the art will
Understand, the following example is merely to illustrate the present invention, and is not construed as limiting the scope of the invention.It is not specified in embodiment specific
Condition person carries out according to conventional conditions or manufacturer's recommended conditions.
Unless otherwise indicated, profession used herein and meaning phase known to scientific term and one skilled in the art
Together.In addition, any method similar to or equal to what is recorded or material can also be applied in the present invention.
As follows in (a)-(d) any substance preparation for diagnose or the product of auxiliary diagnosis heart disease in answer
With:
(a) miR-153-3p, nucleotide sequence is as shown in SEQ ID NO.1:
5'-UUGCAUAGUCACAAAAGUGAUC-3'；
(b) there is the nucleotide sequence of 70% or more homology with the nucleotide sequence of (a)；
(c) nucleotide sequence of miR-153-3p is transcribed, sequence is as shown in SEQ ID NO.8:
5'-TTGCATAGTCACAAAAGTGATC-3'；
(d) there is the nucleotide sequence of 70% or more homology with the nucleotide sequence of (c).
Heart failure is often the terminal developing stage of various heart diseases, and the cardiac myocyte hypertrophy of cellular level and
The myocardial hypertrophy of tissue level is the early stage characterization of the increased heart disease of many loads.And the myocardial hypertrophy of physiological is one
Determine to be adaptability in degree, but pathologic myocardial hypertrophy often eventually develops into heart failure, in cellular level
On performance be that cardiac muscle cell occurs loose, death then and then just occurs.Inventor has found miR- by research for the first time
153-3p participates in adjusting the heart by forming the signal path of NFATC3/miR-153-3p/Mfn1 by influencing chondriokinesis
Myocyte hypertrophy.Therefore, miR-153-3p can be used as early diagnosis or the auxiliary diagnosis marker of heart disease, realize heart
The early diagnosis early treatment of disease, may be implemented diagnosis or auxiliary diagnosis for the kit of miR-153-3p detection；In addition, invention
People's discovery may be implemented just to intervene early stage cardiac muscle cell occurs loose, realize heart by inhibiting miR-153-3p
The early stage of disease effectively prevents or treats.So the nucleotide sequence of miR-153-3p and transcription miR-153-3p can answer
For diagnose or auxiliary diagnosis heart disease in, and can also be used as therewith with the nucleotide sequence of 70% or more homology
Novel targets application, the present invention in, preferably with miR-153-3p or transcribe miR-153-3p nucleotide sequence have 80% with
The nucleotide sequence of upper homology, the still more preferably nucleotide sequence for 90% or more homology.
In being preferably carried out mode, heart disease includes myocardial infarction, treating myocardial ischemia damage, myocardial hypertrophy, heart failure
It exhausts, at least one of myocardial fibrosis or cardiomyopathy.
In being preferably carried out mode, product includes kit.Substance containing detection miR-153-3p in the kit,
The detection of miR-153-3p expression may be implemented, detection substance for example can be probe or primer etc..
As follows in (a)-(d) chaff interferent of any substance in preparing product for preventing or treating heart disease
Using:
(a) miR-153-3p, nucleotide sequence is as shown in SEQ ID NO.1:
5'-UUGCAUAGUCACAAAAGUGAUC-3'；
(b) there is the nucleotide sequence of 70% or more homology with the nucleotide sequence of (a)；
(c) nucleotide sequence of miR-153-3p is transcribed, sequence is as shown in SEQ ID NO.8:
5'-TTGCATAGTCACAAAAGTGATC-3'；
(d) there is the nucleotide sequence of 70% or more homology with the nucleotide sequence of (c).
Since miR-153-3p is by forming NFATC3/miR-153-3p/Mfn1 signal path, mitochondria is influenced to adjust
Cardiac myocyte hypertrophy, so the biological function by inhibiting miR-153-3p, adjustable signal path, to alleviate cardiac muscle
Cellular mast.It is understood that the chaff interferent of miR-153-3p signified in the present invention, which refers to, can inhibit miR-153-3p
The substance of biological function, inventor's research, which has been found that, inhibits miR-153-3p, can significantly alleviate cardiac myocyte hypertrophy.This
Outside, in addition to miR-153-3p, the nucleotide sequence of miR-153-3p is transcribed, and there is the nucleosides of 70% or more homology with the two
Acid sequence can be used as novel targets and inhibit its biological function by chaff interferent, realize prevention or treatment heart disease,
In being preferably carried out mode, chaff interferent includes (a)-(d) in any substance GEM 132.
In being preferably carried out mode, the sequence of the GEM 132 of miR-153-3p is as shown in SEQ ID NO.2, miR-
The GEM 132 of 153-3p: 5 '-GAUCACUUUUGUGACUAUGCAA-3 ' (SEQ ID NO.2).
In being preferably carried out mode, the GEM 132 of miR-153-3p has chemical modification, wherein chemical modification can
Think phosphoric acid backbone modification, ribose modification, base modification or lock nucleic acid modification etc., preferably ribose is modified, further preferably
For the modification of each 2 ' position methoxyl group of base, chemical modification can be improved the stability of GEM 132, delay to degrade.
In being preferably carried out mode, heart disease includes myocardial infarction, treating myocardial ischemia damage, myocardial hypertrophy, heart failure
It exhausts, at least one of myocardial fibrosis or cardiomyopathy.
In being preferably carried out mode, product includes kit, drug, health care product or food.
It is a kind of for diagnosing or the kit of auxiliary diagnosis heart disease, kit includes the object for detecting miR-153-3p
Matter, the sequence of miR-153-3p is as shown in SEQ ID NO.1；
MiR-153-3p:5 '-UUGCAUAGUCACAAAAGUGAUC-3 ' (SEQ ID NO.1).
It is a kind of for preventing or treating the product of heart disease, including the chaff interferent in above-mentioned application.
In being preferably carried out mode, product includes kit, drug, health care product or food.
In being preferably carried out mode, drug further includes pharmaceutically acceptable carrier or auxiliary material.
Preferably, the administration mode of drug is selected from oral, intravenous injection, intramuscular injection, intracoronary injection or direct
Myocardial injection.
Present invention will be further explained by specific examples below, it should be understood, however, that, these embodiments are only
It is used, is but should not be understood as present invention is limited in any form for being described in more detail.
In the present embodiment, we use C57 mouse and Wistar rat.In the cardiac myocyte hypertrophy of cellular level
Isoprel (ISO) induced pathologies cardiac myocyte hypertrophy is used in model, in the myocardial hypertrophy model of animal level
The same cardiac myocyte hypertrophy using ISO induction animal level.In cellular level, we use cell surface product, ANP and β-
Mark of the mRNA expression of MHC as cardiac myocyte hypertrophy.In animal level, we use heart weight weight ratio and transversal
Face cell area, cardiac muscular tissue collagenzation be horizontal, ANP mRNA expression is detected.
Unless specifically stated otherwise, various experimental methods and operation involved in following embodiment, including the primary heart of rat suckling mouse
The preparation and culture of myocyte, the building of adenovirus and the dosage for infecting cardiac muscle cell, cell surface product measurement, sarcomere structure
Dyeing, heart paraffin section, HE dyeing and WGA dyeing, the detection method of heart weight ratio, cardiac function in detail chat
It states, building, amplification and the transfection of carrier, cell dyeing etc., reference can be made to following documents:
1.Tan WQ,Wang K,Lv DY,Li PF.Foxo3a inhibits cardiomyocyte hypertrophy
through transactivating catalase.The Journal of biological chemistry.2008；
283:29730-29739；
2.Wang K,Long B,Zhou J,Li PF.Mir-9and nfatc3regulate myocardin in
cardiac hypertrophy.The Journal of biological chemistry.2010；285:11903-11912；
3.Lin Z,Murtaza I,Wang K,Jiao J,Gao J,Li PF.Mir-23a functions
downstream of nfatc3 to regulate cardiac hypertrophy.Proceedings of the
National Academy of Sciences of the United States of America.2009；106:12103-
12108；
4.Wang K,Long B,Jiao JQ,Wang JX,Liu JP,Li Q,Li PF.Mir-484regulates
mitochondrial network through targeting fis1.Nature communications.2012；3:
781。
Which is hereby incorporated by reference for above-mentioned document.
Cellular level miRNA-153-3p expression detects during 1 ISO inducing cardiomyocytes of embodiment are loose
During we detect that ISO inducing cardiomyocytes are loose first, the expression contents of miR-153-3p constantly increase
Add (Fig. 1).In this embodiment, using the established method culture rat suckling mouse primary cardiomyocytes in this laboratory, ISO is utilized
The rat suckling mouse primary cardiomyocytes of processing establish cardiac myocyte hypertrophy model, specifically, to rat cream in cell incubator
Mouse primary cardiomyocytes are cultivated, and culture scale is 10cm culture dish, and the cell concentration of each culture dish is about 1 × 106It is a, training
The feeding time continues 0,8,18,24 hour.RNA is extracted with the difference of incubation time, and is examined using Real-Time Fluorescent Quantitative PCR Technique
Survey the mRNA expression of miRNA-153-3p.
Specifically, PCR amplification miRNA-153-3p coded sequence
(CGGTGTCATTTTTGTGACGTTGCAGCTAGTAATATGAGCCCAGTTGCATAGTCACAAAAGTGATCAT
TG, SEQ ID NO:3) and its each nearly 200 bp in upstream and downstream both ends sequence, amplified fragments about 511bp, specifically: (
The wherein coded sequence that italic leukorrhagia marking is miRNA-153-3p；Remaining is its upstream and downstream sequence
Column, blacken and leukorrhagia marking is upstream and downstream primer sequence, and 50 μ l, PCR condition of PCR system is as follows: 95 DEG C 3min mono-
Circulation；95 DEG C of 30sec, 54 DEG C of 30sec, 72 DEG C of 1min are recycled for 30 totally；Last 72 DEG C of extensions 10min, PCR primer design such as
Under:
Upstream primer: 5'-TCTCAGCAGGCCTAGAGTGT-3'(SEQ ID NO:5)；
Downstream primer: 5'-GCCCCAAGAAGGAACCGTTA-3'(SEQ ID NO:6).
The miRNA-153-3p expression that detects is as shown in Figure 1, in the section of ISO processing 0h-24h, miRNA-
The expression of 153-3p is significantly raised.
2 miRNA-153-3p GEM 132 of embodiment effectively inhibits the experiment of cardiac myocyte hypertrophy
Cardiac muscle cell in this experiment using originally culture in embodiment 1 is model.To cardiac muscle cell, (cell concentration is about 1
×106) carry out (the SEQ ID NO.2) transfection of miRNA-153-3p GEM 132 processing (pass through liposome lipfectin3000
Transfected according to kit operational manual, be purchased from Invitrogen company), it is right in cell culture after transfection 24 hours
The cell carries out ISO culture processing 24 hours, with inducing cell hypertrophy.Meanwhile without miRNA-153-3p GEM 132
The primary cardiomyocytes of transfection are negative control, detect the expression of endogenous miRNA-153-3p, show miRNA-153-3p
GEM 132 can effectively inhibit the endogenous expression (Fig. 2A) of miRNA-153-3p.And myocardial hypertrophy is carried out to cardiac muscle cell and is referred to
Target detection, such as cell surface product (see Fig. 2 B) and hypertrophy marker (including ANP and β-MHC mRNA) expression
It detects (see Fig. 2 C).Experimental result is as shown in Fig. 2 B and Fig. 2 C, through miRNA-153-3p GEM 132 (anta-153-
3p) the long-pending and loose marker expression level of the cell surface transfected is right significantly lower than the feminine gender of miRNA-153-3p GEM 132
According to group (anta-NC), this proves that miRNA-153-3p GEM 132 can effectively inhibit cardiac muscle cell's fertilizer that ISO is induced
Greatly.
3 miRNA-153-3p GEM 132 of embodiment effectively inhibits mouse model cardiac myocyte hypertrophy to test
The GEM 132 (SEQ ID NO.2) of this experiment miRNA-153-3p used is the miRNA- by modification
153-3p GEM 132, modification mode are to have carried out 2 '-methoxies to each base of miRNA-153-3p GEM 132
Base is modified to increase the stability of miRNA-153-3p GEM 132 in vivo.MiRNA-153-3p GEM 132 is repaired
Decorations and synthesis are completed by Shanghai Ji Ma company.
The injection of mouse underwent coronary or tail vein injection miRNA-153-3p GEM 132 can significantly inhibit cardiac muscle
Cellular mast.Using C57 mouse as experimental subjects, the feminine gender of miRNA-153-3p GEM 132 and it is injected as follows
It compares (NC)
(5 '-CAGUACUUUUGUGUAGUACAA-3 ' (SEQ IDNO:7), and each base has carried out 2 '-first
Oxygroup modification, by Shanghai, Ji Ma company is synthesized).
For inducing heart hypertrophy, by the osmotic mini-pump (1002 type of Alzet, Alza Corp.) of implantation to small
Mouse injects the salt water of ISO (40mg/kg/ days) or same volume, continues 14 days.It is right in order to shift antagomir or negative in vivo
According to (anta-NC), mouse by ISO and miR-153-3p antagomir (30mg/kg) or anta-NC (30mg/kg) together
Infusion.At the end for the treatment of phase, osmotic pumps are removed by operation.After 14 days to all mouse carry out echocardiogram measurement and
Hypertrophy analysis.
As a result as shown in Fig. 3 A- Fig. 3 E, miRNA-153-3p GEM 132 can reduce in the mouse model that ISO is induced
Cardiac myocyte hypertrophy enhances heart function.Myocardial hypertrophy indicator index heart weight weight ratio reduces (Fig. 3 A), and cell cross section product reduces
(Fig. 3 B), myocardium ANP expression quantity reduce (Fig. 3 C), and myocardial collagen content reduces (Fig. 3 D), and cardiac ejection fraction increases (Fig. 3 E).
Although illustrate and describing the present invention with specific embodiment, it will be appreciated that without departing substantially from of the invention
Many other change and modification can be made in the case where spirit and scope.It is, therefore, intended that in the following claims
Including belonging to all such changes and modifications in the scope of the invention.
SEQUENCE LISTING
<110>University Of Qingdao
<120>application of miR-153-3p and its chaff interferent and product
<160> 8
<170> PatentIn version 3.5
<210> 1
<211> 22
<212> RNA
<213>artificial sequence
<400> 1
uugcauaguc acaaaaguga uc 22
<210> 2
<211> 22
<212> RNA
<213>artificial sequence
<400> 2
gaucacuuuu gugacuaugc aa 22
<210> 3
<211> 69
<212> DNA
<213>artificial sequence
<400> 3
cggtgtcatt tttgtgacgt tgcagctagt aatatgagcc cagttgcata gtcacaaaag 60
tgatcattg 69
<210> 4
<211> 511
<212> DNA
<213>artificial sequence
<400> 4
tctcagcagg cctagagtgt gtgtcaggca cccaagatgt gtaattaact gttgctggag 60
cccagggggc atacatttac actttaaaga gaaactgcta agagataatt agagtcacat 120
gtgagggctt ggctctacaa acctctcttc tctccccagt ctccgtgttc tctctccctc 180
cctctttccc tccctccctc ttctcctctc tgcacctctt gctgtgttcc atgcatccac 240
taacgctgct cactgtcaaa ccgacaaacc cttactttgc cagctactta gcggtggccg 300
gtgtcatttt tgtgacgttg cagctagtaa tatgagccca gttgcatagt cacaaaagtg 360
atcattggaa actgtgactg cagcagggac atgggggccc ctctctgagc ctctaacgac 420
ctcacctgac tttgcttgct gttcgtttgc atggcgactc actcagtgac caaagggttg 480
gtttgtattg ctaacggttc cttcttgggg c 511
<210> 5
<211> 20
<212> DNA
<213>artificial sequence
<400> 5
tctcagcagg cctagagtgt 20
<210> 6
<211> 20
<212> DNA
<213>artificial sequence
<400> 6
gccccaagaa ggaaccgtta 20
<210> 7
<211> 21
<212> RNA
<213>artificial sequence
<400> 7
caguacuuuu guguaguaca a 21
<210> 8
<211> 22
<212> DNA
<213>artificial sequence
<400> 8
ttgcatagtc acaaaagtga tc 22
Claims (10)
1. in following (a)-(d) any substance preparation for diagnose or the product of auxiliary diagnosis heart disease in application:
(a) miR-153-3p, nucleotide sequence is as shown in SEQ ID NO.1:
5'-UUGCAUAGUCACAAAAGUGAUC-3'；
(b) there is the nucleotide sequence of 70% or more homology with the nucleotide sequence of (a)；
(c) nucleotide sequence of miR-153-3p is transcribed, sequence is as shown in SEQ ID NO.8:
5'-TTGCATAGTCACAAAAGTGATC-3'；
(d) there is the nucleotide sequence of 70% or more homology with the nucleotide sequence of (c).
2. application according to claim 1, which is characterized in that the heart disease includes myocardial infarction, myocardial ischemia damage
At least one of wound, myocardial hypertrophy, heart failure, myocardial fibrosis or cardiomyopathy.
3. application according to claim 1, which is characterized in that the product includes kit.
4. the chaff interferent of any substance is preparing answering in the product for preventing or treating heart disease in following (a)-(d)
With:
(a) miR-153-3p, nucleotide sequence is as shown in SEQ ID NO.1:
5'-UUGCAUAGUCACAAAAGUGAUC-3'；
(b) there is the nucleotide sequence of 70% or more homology with the nucleotide sequence of (a)；
(c) nucleotide sequence of miR-153-3p is transcribed, sequence is as shown in SEQ ID NO.8:
5'-TTGCATAGTCACAAAAGTGATC-3'；
(d) there is the nucleotide sequence of 70% or more homology with the nucleotide sequence of (c).
5. application according to claim 4, which is characterized in that the chaff interferent includes (a)-(d) in any substance
GEM 132；
Preferably, the sequence of the GEM 132 of the miR-153-3p is as shown in SEQ ID NO.2；
The GEM 132 of miR-153-3p: 5 '-GAUCACUUUUGUGACUAUGCAA-3 ' (SEQ ID NO.2)；
Preferably, the GEM 132 of the miR-153-3p has chemical modification；
Preferably, the chemical modification includes that phosphoric acid backbone modification, ribose modification, base modification or lock nucleic acid are modified, further
Preferably ribose is modified, and is still more preferably the modification of each 2 ' position methoxyl group of base.
6. application according to claim 4 or 5, which is characterized in that the heart disease includes myocardial infarction, myocardial ischemia
At least one of damage, myocardial hypertrophy, heart failure, myocardial fibrosis or cardiomyopathy；
Preferably, the product includes kit, drug, health care product or food.
7. a kind of for diagnosing or the kit of auxiliary diagnosis heart disease, which is characterized in that the kit includes detection
The substance of miR-153-3p, the sequence of miR-153-3p is as shown in SEQ ID NO.1；
MiR-153-3p:5 '-UUGCAUAGUCACAAAAGUGAUC-3 ' (SEQ ID NO.1).
8. a kind of for preventing or treating the product of heart disease, which is characterized in that the product includes claim 4-6 any
Chaff interferent in the item application.
9. product according to claim 8, which is characterized in that the product includes kit, drug, health care product or food
Product.
10. product according to claim 9, which is characterized in that the drug further include pharmaceutically acceptable carrier or
Auxiliary material；
Preferably, the administration mode of the drug is selected from oral, intravenous injection, intramuscular injection, intracoronary injection or direct
Myocardial injection.
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Citations (1)
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|---|---|---|---|---|
| US20150197809A1 (en) * | 2014-01-13 | 2015-07-16 | Trustees Of Boston University | Methods and assays relating to huntingtons disease and parkinson's disease |
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2019
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20150197809A1 (en) * | 2014-01-13 | 2015-07-16 | Trustees Of Boston University | Methods and assays relating to huntingtons disease and parkinson's disease |
Non-Patent Citations (4)
| Title |
|---|
| SHUYAO TANG ET AL.: "An artificial lncRNA targeting multiple miRNAs overcomes sorafenib resistance in hepatocellular carcinoma cells", 《ONCOTARGET》 * |
| YUHAI ZOU ET AL.: "miR-153 regulates apoptosis and autophagy of cardiomyocytes by targeting Mcl-1", 《MOLECULAR MEDICINE REPORTS》 * |
| 冯强等: "非编码核糖核酸参与心脏钙稳态调控机制的研究现状", 《中国临床药理学杂志》 * |
| 张丽霞等: "MiR -153-3p 调控异丙肾上腺素诱导的心肌肥大机制研究", 《转化医学杂志》 * |
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