CN106267237A - A kind of genomic medicine treating hepatocarcinoma and metabolism disorder - Google Patents
A kind of genomic medicine treating hepatocarcinoma and metabolism disorder Download PDFInfo
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- CN106267237A CN106267237A CN201610879822.0A CN201610879822A CN106267237A CN 106267237 A CN106267237 A CN 106267237A CN 201610879822 A CN201610879822 A CN 201610879822A CN 106267237 A CN106267237 A CN 106267237A
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- 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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Abstract
The invention discloses a kind of genomic medicine treating hepatocarcinoma and metabolism disorder, the genomic medicine of the present invention is the gland relevant viral vector carrying microRNA26a gene.The present invention can suppress DEN induction hepatocarcinoma to develop.It addition, the present invention can strengthen insulin resistant ability and glucose tolerance, improve the insulin sensitivity of liver, thus significantly inhibit the metabolism disorder that obesity causes.
Description
Technical field
The present invention relates to a kind of genomic medicine treating hepatocarcinoma and metabolism disorder.
Background technology
MicroRNA is the noncoding RNA that a class is little, rises in bioprocesss such as growing at cell, grow, break up, be dead
Important effect, meanwhile, microRNA almost take part in hemopoietic, insulin secretion, nervous system composition and the mankind
The process of each vital movement such as growth of cancer cells.Sequence analysis shows, has the human gene of more than 1/3 to be directly subject to
The regulation and control of microRNA, and increasing test data shows that microRNA also has a lot of function undiscovered.
MicroRNA has the effect of tumor-inhibiting factor and oncogene, the imbalance of microRNA and gene mutation or epigenetic variation
Relevant.
Recombinant adeno-associated virus (rAAV) is already used to treat multiple heredopathia and minority metabolic disease, has safety,
Efficiently, the advantage that immunotoxicity is low.
Gene medicine currently with recombinant adeno-associated virus treatment cancer and metabolic disease is less.People cannot be met
Demand.
Summary of the invention
In order to improve the problems referred to above, it is an object of the invention to provide a kind of gene medicine treating hepatocarcinoma and metabolism disorder
Thing.
To achieve these goals, the technical solution used in the present invention is as follows:
A kind of genomic medicine treating hepatocarcinoma and metabolism disorder, described genomic medicine is the gland carrying microRNA26a gene
Related viral vectors.
Further, the sequence information of described microRNA26a gene is as shown in SEQ ID NO.1.
Select as one, the sequence information of the microRNA26a gene of the present invention concretely SEQ ID NO.3.
Yet further, described microRNA26a gene forms the miR-26a sequence of maturation in cell, and its sequence is believed
Breath is as shown in SEQ ID NO.2.
The present invention has the following advantages and beneficial effect:
1, the present invention can suppress DEN-induction hepatocarcinoma to develop.
2, the present invention can strengthen insulin resistant ability and glucose tolerance, improves the insulin sensitivity of liver
Property, thus significantly inhibit the metabolism disorder that obesity causes.
Accompanying drawing explanation
Fig. 1 is the liver comparison figure of mice.
Fig. 2 is mouse interior tumor number comparison figure.
Fig. 3 is the Mice Body interior diameter tumor number comparison figure more than 5cm.
Fig. 4 is miR-26a expression comparison figure in liver organization.
Fig. 5 is insulin resistant experimental result comparison figure.
Fig. 6 is glucose tolerance experimental results comparison figure.
Fig. 7 is insulin sensitivity result of the test comparison figure in Mice Body.
Detailed description of the invention
Below in conjunction with embodiment, the invention will be further described, but embodiments of the present invention are not limited to following enforcement
Example.
Embodiment
A kind of genomic medicine treating hepatocarcinoma and metabolism disorder, described genomic medicine is for carrying microRNA26a gene
Gland relevant viral vector;Wherein, the sequence information of described microRNA26a gene is as shown in SEQ ID NO.1.
What deserves to be explained is, described microRNA26a gene forms the miR-26a sequence of maturation, its sequence in cell
Information is as shown in SEQ ID NO.2.
The present invention is to use prior art to be packed and on gland relevant viral vector by microRNA26a gene, so
This does not repeats.
Mice is tested by medicine as follows that use the present invention:
1, the inhibition to hepatocarcinoma:
Experimental technique: take 4 week old C57/BL6 normal mouse 20, random point 2 groups, 1. AVV vehicle Control group;②AAV-miR-
26a process group, tail vein injection is administered once.After two weeks, high fat diet (HFD) feeds mice 16 weeks, lumbar injection carcinogen two
Ethyl nitrosamine (DEN) (100mg/kg Mouse Weight), after 2 weeks, accepts lumbar injection carcinogenic promoting agent TCPOBOP 6 times every other week
(3mg/kg Mouse Weight), checked hepatocarcinoma situation after 4-5 month, and result is as shown in Figures 1 to 3.From figure, result understands, and AAV is situated between
The miR-26a process LAN led can significantly inhibit DEN-induction hepatocarcinoma to be developed.
2, the inhibition of the metabolism disorder that obesity is caused:
Experimental technique: take 4 week old C57/BL6 normal mouse 20, random point 2 groups, i.e. AAV vehicle Control group and AAV-miR-
26a process group.Two groups of mices pass through tail vein injection AVV carrier 1 time.After two weeks, high fat diet (HFD) feeds mice 16 weeks,
Carry out insulin resistant experiment (ITT, insulin dose 1U/kg Mouse Weight) and glucose sugar tolerance test (GTT, Fructus Vitis viniferae respectively
Sugar dosage 2g/kg Mouse Weight), the miR-26a process LAN of detection AAV mediation is to insulin resistant ability and glucose-tolerant energy
The impact of power.Meanwhile, respectively randomly selecting 3 mices in two groups, (insulin dose 1U/kg is little for postcava insulin injection
Mus body weight) or normal saline, to collect liver and carry out western hybridization, the miR-26a process LAN of detection AAV mediation is to islets of langerhans
The impact of element sensitivity.Sacrificing mice, the miR-26a process LAN situation of QRT-PCR method quantitative analysis AAV mediation, result is such as
Shown in Fig. 4~7.From figure, result understands, and AAV carrier can significantly improve miR-26a expression in liver organization.And, AAV
The miR-26a process LAN of mediation can be obviously enhanced insulin resistant ability and the glucose tolerance of mice, improves liver
Insulin sensitivity, thus significantly inhibit the metabolism disorder that obesity causes.
It should be noted that, above example is only in order to illustrative not limiting technical scheme, although with reference to upper
State embodiment the present invention has been described in detail, it will be understood by those within the art that: still can be to the present invention
Modifying or equivalent, any modification or partial replacement without departing from the spirit and scope of the present invention, it all should be contained
Cover in scope of the presently claimed invention.
SEQUENCE LISTING
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agaaattctc tcccgaggga atgaagccac aggagccaag agcaggagga ccaaggccct 240
ggcgaaggcc gtggcctcgt tcaagtaatc caggataggc tgtgcaggtc ccaatgggcc 300
tattcttggt tacttgcacg gggacgcggg cctggacgcc ggcatccggg ctcaggaccc 360
ccctctctgc cagaggcacc aacaccagag ttcacaaatc agtctcctgc cctttgcatg 420
tagcaaagct tgctttccaa gcaggactcc cagggtgact gaggactaca ggccacaccc 480
gtttgctggc aacgaggagt cttgtgggca aagtgggagt ctgcagctgt tgcagccaca 540
ggccctgccc tcagccctac cccagcctcc cagctcc 577
Claims (3)
1. the genomic medicine treating hepatocarcinoma and metabolism disorder, it is characterised in that described genomic medicine is for carrying
The gland relevant viral vector of microRNA26a gene.
A kind of genomic medicine treating hepatocarcinoma and metabolism disorder the most according to claim 1, it is characterised in that described
The sequence information of microRNA26a gene is as shown in SEQ ID NO.1.
A kind of genomic medicine treating hepatocarcinoma and metabolism disorder the most according to claim 2, it is characterised in that described
MicroRNA26a gene forms the miR-26a sequence of maturation in cell, and its sequence information is as shown in SEQ ID NO.2.
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Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN111248148A (en) * | 2018-12-03 | 2020-06-09 | 凯斯艾生物科技(苏州)有限公司 | Construction method of rat model with severe non-alcoholic chronic steatohepatitis on non-diabetic basis |
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CN102451474A (en) * | 2010-10-29 | 2012-05-16 | 中国人民解放军第二军医大学 | Antitumor effect, implementation method and usage of miRNA (micro-ribonucleic acid) |
CN102776185A (en) * | 2011-05-06 | 2012-11-14 | 复旦大学附属中山医院 | Liver cancer diagnostic marker composed of blood plasma microRNA (micro ribonucleic acid) and new method for diagnosing liver cancer |
CN103088061A (en) * | 2013-01-15 | 2013-05-08 | 中国科学院微生物研究所 | Application of RNA and carrier in preparation of product for preventing and/or treating liver cancer |
CN103394099A (en) * | 2013-08-06 | 2013-11-20 | 哈尔滨医科大学 | Application of microRNA-26a in preparation of drug for prevention or treatment of pulmonary fibrosis |
CN104152452A (en) * | 2014-08-19 | 2014-11-19 | 中国人民解放军总医院第一附属医院 | Blood miRNA marker related to liver cancer and application thereof |
-
2016
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Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
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CN102451474A (en) * | 2010-10-29 | 2012-05-16 | 中国人民解放军第二军医大学 | Antitumor effect, implementation method and usage of miRNA (micro-ribonucleic acid) |
CN102319247A (en) * | 2010-11-25 | 2012-01-18 | 上海聚类生物科技有限公司 | Mir-26a-targeted anti-osteosarcoma small molecular compound |
CN102776185A (en) * | 2011-05-06 | 2012-11-14 | 复旦大学附属中山医院 | Liver cancer diagnostic marker composed of blood plasma microRNA (micro ribonucleic acid) and new method for diagnosing liver cancer |
CN103088061A (en) * | 2013-01-15 | 2013-05-08 | 中国科学院微生物研究所 | Application of RNA and carrier in preparation of product for preventing and/or treating liver cancer |
CN103394099A (en) * | 2013-08-06 | 2013-11-20 | 哈尔滨医科大学 | Application of microRNA-26a in preparation of drug for prevention or treatment of pulmonary fibrosis |
CN104152452A (en) * | 2014-08-19 | 2014-11-19 | 中国人民解放军总医院第一附属医院 | Blood miRNA marker related to liver cancer and application thereof |
Non-Patent Citations (3)
Title |
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FU X等: "MicroRNA-26a regulates insulin sensitivity and metabolism of glucose and lipids", 《J CLIN INVEST.》 * |
JANAIAH KOTA等: "Therapeutic microRNA delivery suppresses tumorigenesis in a murine liver cancer model.", 《CELL》 * |
XIN YANG等: "MicroRNA-26a Suppresses Tumor Growth and Metastasis of Human Hepatocellular Carcinoma by Targeting Interleukin-6-Stat3 Pathway", 《HEPATOLOGY》 * |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN111248148A (en) * | 2018-12-03 | 2020-06-09 | 凯斯艾生物科技(苏州)有限公司 | Construction method of rat model with severe non-alcoholic chronic steatohepatitis on non-diabetic basis |
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