CN116726181A - Use of agent for inhibiting NAT9 gene expression - Google Patents
Use of agent for inhibiting NAT9 gene expression Download PDFInfo
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- CN116726181A CN116726181A CN202310995413.7A CN202310995413A CN116726181A CN 116726181 A CN116726181 A CN 116726181A CN 202310995413 A CN202310995413 A CN 202310995413A CN 116726181 A CN116726181 A CN 116726181A
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- 230000014509 gene expression Effects 0.000 title claims abstract description 18
- 230000002401 inhibitory effect Effects 0.000 title claims abstract description 11
- 101150090948 nat9 gene Proteins 0.000 title abstract description 3
- 201000008968 osteosarcoma Diseases 0.000 claims abstract description 33
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 23
- 206010027476 Metastases Diseases 0.000 claims abstract description 12
- 230000009401 metastasis Effects 0.000 claims abstract description 12
- 239000003814 drug Substances 0.000 claims abstract description 11
- 239000003795 chemical substances by application Substances 0.000 claims description 13
- 108090000623 proteins and genes Proteins 0.000 claims description 8
- 238000012226 gene silencing method Methods 0.000 claims description 4
- 239000003112 inhibitor Substances 0.000 claims description 4
- 230000005764 inhibitory process Effects 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 230000002265 prevention Effects 0.000 claims description 3
- 230000030279 gene silencing Effects 0.000 claims description 2
- 239000000463 material Substances 0.000 claims description 2
- 108091028043 Nucleic acid sequence Proteins 0.000 claims 2
- 229940079593 drug Drugs 0.000 abstract 1
- 210000004027 cell Anatomy 0.000 description 27
- 230000006907 apoptotic process Effects 0.000 description 12
- XJMOSONTPMZWPB-UHFFFAOYSA-M propidium iodide Chemical compound [I-].[I-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CCC[N+](C)(CC)CC)=C1C1=CC=CC=C1 XJMOSONTPMZWPB-UHFFFAOYSA-M 0.000 description 6
- 230000012292 cell migration Effects 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 230000004083 survival effect Effects 0.000 description 4
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 3
- 210000000170 cell membrane Anatomy 0.000 description 3
- 230000004663 cell proliferation Effects 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 230000035755 proliferation Effects 0.000 description 3
- 239000012096 transfection reagent Substances 0.000 description 3
- 102000004121 Annexin A5 Human genes 0.000 description 2
- 108090000672 Annexin A5 Proteins 0.000 description 2
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 2
- 101000602350 Homo sapiens N-acetyltransferase 9 Proteins 0.000 description 2
- 102100037155 N-acetyltransferase 9 Human genes 0.000 description 2
- 239000006285 cell suspension Substances 0.000 description 2
- 238000002512 chemotherapy Methods 0.000 description 2
- 230000005012 migration Effects 0.000 description 2
- 238000013508 migration Methods 0.000 description 2
- 239000002773 nucleotide Substances 0.000 description 2
- 125000003729 nucleotide group Chemical group 0.000 description 2
- 108050008874 Annexin Proteins 0.000 description 1
- 102000000412 Annexin Human genes 0.000 description 1
- 101000699762 Homo sapiens RNA 3'-terminal phosphate cyclase Proteins 0.000 description 1
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
- 101710202061 N-acetyltransferase Proteins 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- 102100029143 RNA 3'-terminal phosphate cyclase Human genes 0.000 description 1
- IWUCXVSUMQZMFG-AFCXAGJDSA-N Ribavirin Chemical compound N1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 IWUCXVSUMQZMFG-AFCXAGJDSA-N 0.000 description 1
- 239000000980 acid dye Substances 0.000 description 1
- 238000011226 adjuvant chemotherapy Methods 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000000692 anti-sense effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
- 229960004316 cisplatin Drugs 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 229960004679 doxorubicin Drugs 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000000684 flow cytometry Methods 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000001394 metastastic effect Effects 0.000 description 1
- 206010061289 metastatic neoplasm Diseases 0.000 description 1
- 229960000485 methotrexate Drugs 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 238000011272 standard treatment Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Physical Education & Sports Medicine (AREA)
- Epidemiology (AREA)
- Rheumatology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biochemistry (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Molecular Biology (AREA)
- Oncology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention provides an application of a reagent for inhibiting NAT9 gene expression, belonging to the technical field of medicines. The invention can inhibitNAT9The gene expression reagent is used as a medicament for inhibiting osteosarcoma and inhibiting metastasis of osteosarcoma, and provides a new choice for clinically treating osteosarcoma and metastasis thereof.
Description
Technical Field
The invention belongs to the field of medical engineering, and in particular relates to an inhibition methodNAT9Use of a reagent for gene expression.
Background
Osteosarcoma is a common primary bone malignancy, which occurs in children and adolescents, and the current standard treatment is a combination of neoadjuvant chemotherapy-surgery-adjuvant chemotherapy based on a regimen comprising doxorubicin, cisplatin, and large doses of methotrexate (MAP regimen). Although perioperative chemotherapy greatly improves the 5-year survival rate and the limb protection rate of patients with osteosarcoma, the 5-year survival rate of patients with limited period is 60% -70%, the survival benefit brought by chemotherapy does not obtain further breakthrough in more than 40 years. 10% -15% of osteosarcoma patients are accompanied with metastasis at the initial diagnosis, the most common metastasis site is lung, the survival rate of the patients with metastatic or recurrent osteosarcoma is only 20% in 5 years, the prognosis is extremely poor, and improvement is needed in the current state of treatment.
NAT9UniProt accession number Q9BTE0, N-acetyltransferase, is a member of the NAT family of genes. Not seeNAT9Reports on osteosarcoma.
Disclosure of Invention
The invention aims to provide inhibitionNAT9The application of gene expression reagent in inhibiting osteosarcoma and its metastasis.
The invention provides a method for inhibitingNAT9Use of an agent for gene expression in the manufacture of a medicament for the prevention and/or treatment of osteosarcoma.
The invention also provides inhibition ofNAT9Preparation of agents for reducing Gene expressionUse in medicine for osteosarcoma metastasis.
Wherein the agent is a knockoutNAT9And (3) a reagent of a gene. Preferably, the reagent comprises a nucleotide sequence shown in SEQ ID NO. 1-2.
Wherein the reagent is a reagent for causingNAT9Agents for gene silencing.
Wherein the reagent isNAT9Inhibitors of genes.
The invention also provides a medicament for inhibiting osteosarcoma or osteosarcoma metastasis, which comprises inhibitingNAT9A reagent for gene expression and pharmaceutically acceptable auxiliary materials.
Wherein the agent is a knockoutNAT9Gene reagent and gene expression systemNAT9Agents or agents for gene silencingNAT9Inhibitors of genes.
Wherein the reagent comprises a nucleotide sequence shown in SEQ ID NO. 1-2.
The invention has the beneficial effects that the invention is knocked downNAT9Can remarkably inhibit proliferation of osteosarcoma cells, remarkably promote apoptosis of osteosarcoma cells, inhibit migration of osteosarcoma cells, and inhibit proliferation of osteosarcoma cellsNAT9The gene expression reagent is used as a medicament for inhibiting osteosarcoma and inhibiting metastasis of osteosarcoma, and provides a new choice for clinically treating osteosarcoma and metastasis thereof.
It should be apparent that, in light of the foregoing, various modifications, substitutions and alterations can be made herein without departing from the spirit and scope of the invention as defined by the appended claims.
The above-described aspects of the present invention will be described in further detail below with reference to specific embodiments in the form of examples. It should not be understood that the scope of the above subject matter of the present invention is limited to the following examples only. All techniques implemented based on the above description of the invention are within the scope of the invention.
Drawings
FIG. 1NAT9And (5) a graph of gene expression proportion results.
Fig. 2 knockdownNAT9Inhibition of 143b cell proliferation patterns; FIG. A shows the detection of 143b cells after knockdown of NAT9 by a dynamic detectorA growth index; panel B is a graph of cell viability statistics.
Fig. 3 knockdownNAT9A graph of apoptosis promotion 143 b; a is a knockdown NAT9 flow cytometry analysis apoptosis graph, and B is an apoptosis proportion statistical result graph.
Fig. 4 knockdownNAT9Inhibition 143b cell migration profile; a is a stained, perforated cell map, and B is a statistical map of the number of migrating cells.
Detailed Description
The raw materials and equipment used in the invention are all known products and are obtained by purchasing commercial products.
143b cells: osteosarcoma cells purchased from the biological technology Co.Ltd
Lipofectamine ™ 3000 transfection reagent: eukaryotic transfection reagents were purchased from thermosusher under the designation L3000001.
Annexin V-APC/PI apoptosis detection kit: apoptosis was detected. Propidium Iodide (PI) is a nucleic acid dye that does not penetrate intact cell membranes, but cells in the middle and late stages of apoptosis and dead cells due to increased cell membrane permeability, PI can penetrate cell membranes and stain the nucleus with red. By matching Annexin V to PI, cells at different stages of apoptosis can be distinguished. The product number KGA1030, the Yu Kaiji organism was purchased.
Example 1,NAT9Effects of knockout on osteosarcoma
1. Experimental method
(one)NAT9Knock-out
143b Cell line was inoculated in an e-plate96 well plate (DMEM medium) and placed in an RTCA Cell dynamic detector, and sh-NAT9 and transfection reagent were added when the CI (Cell Index, indicator of Cell growth) was 1, to add universal negative control NC-treated cells as controls.
sh-NAT9：
sense CCACGAGTGGATGAAATCA （SEQ ID NO.1）
antisense GGTGCTCACCTACTTTAGT（SEQ ID NO.2）。
shNC group: is a negative transfection control group.
(II) inspection method
Apoptosis: 143b cell knockdownNAT9 After 48h, the cell suspension was collected. The cell suspension was centrifuged for 5 min at 250 g, the supernatant was aspirated, washed once with PBS, centrifuged for 5 min at 250 g, and the collected cell pellet was used for staining. After resuspension of the cells with 500 μl of PBS buffer (prinocetary, cat No. PB 180327), 5 μl of Annexin V was added and gently blown up, followed by addition of 5 μl of PI and mixing; incubate at room temperature for 10 min under light protection, and perform detection analysis using a flow analyser (model: cytoflex manufacturer: beckman) instrument.
Cell migration: serum-free DMEM 200. Mu.L and 2X 10 were added to the Transwell chamber 4 143b cells, 600. Mu.L of 10% serum DMEM was added to the lower chamber at 5% CO 2 The cell incubator was incubated for 24 hours, the cells passing through the membrane pores were stained with 1% crystal violet in a 4% paraformaldehyde fixed cell, photographed under a normal microscope, the number of perforated cells calculated, and the cell mobility calculated.
2. Experimental results
NAT9The result of the gene expression ratio is shown in FIG. 1, the lower the gene expression ratio is, the higher the knocking down efficiency is,NAT9the knockdown efficiency was 64%.
As can be seen from fig. 2, knockdownNAT9Significantly inhibited 143b cell proliferation. As can be seen from fig. 3, knockdownNAT9Significantly promoting 143b apoptosis.
As can be seen from fig. 4, knockdownNAT9Significantly inhibiting 143b cell migration.
The invention knocks down in osteosarcoma cellsNAT9Can significantly inhibit 143b cell proliferation (fig. 2), significantly promote 143b apoptosis (fig. 3), and significantly inhibit 143b cell migration (fig. 4).
In conclusion, the invention is realized by knocking downNAT9Can remarkably inhibit proliferation of osteosarcoma cells, remarkably promote apoptosis of osteosarcoma cells, and remarkably inhibit migration of osteosarcoma cells, which indicates inhibitionNAT9The gene expression reagent can effectively inhibit osteosarcoma and can also inhibit metastasis of osteosarcoma, and has important theoretical and practical significance for clinical osteosarcoma prevention and treatment.
Claims (9)
1. Inhibition ofNAT9Use of an agent for gene expression in the manufacture of a medicament for the prevention and/or treatment of osteosarcoma.
2. Inhibition ofNAT9Use of an agent for gene expression in the manufacture of a medicament for reducing osteosarcoma metastasis.
3. Use according to claim 1 or 2, characterized in that: the reagent is knockdownNAT9And (3) a reagent of a gene.
4. Use according to claim 3, characterized in that: the reagent comprises nucleotide sequences shown in SEQ ID NO. 1-2.
5. Use according to claim 1 or 2, characterized in that: the reagent is to makeNAT9Agents for gene silencing.
6. Use according to claim 1 or 2, characterized in that: the reagent isNAT9Inhibitors of genes.
7. A medicament for inhibiting osteosarcoma or osteosarcoma metastasis, characterized in that: it includes inhibitionNAT9A reagent for gene expression and pharmaceutically acceptable auxiliary materials.
8. A medicament according to claim 7, characterized in that: the reagent is knockdownNAT9Gene reagent and gene expression systemNAT9Agents or agents for gene silencingNAT9Inhibitors of genes.
9. A medicament according to claim 7, characterized in that: the reagent comprises nucleotide sequences shown in SEQ ID NO. 1-2.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310995413.7A CN116726181B (en) | 2023-08-09 | 2023-08-09 | Use of agent for inhibiting NAT9 gene expression |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310995413.7A CN116726181B (en) | 2023-08-09 | 2023-08-09 | Use of agent for inhibiting NAT9 gene expression |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN116726181A true CN116726181A (en) | 2023-09-12 |
| CN116726181B CN116726181B (en) | 2023-10-20 |
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| CN202310995413.7A Active CN116726181B (en) | 2023-08-09 | 2023-08-09 | Use of agent for inhibiting NAT9 gene expression |
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Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003020930A1 (en) * | 2001-08-29 | 2003-03-13 | The Board Of Trustees Of The University Of Illinois | IDENTIFICATION AND USE OF MAMMALIAN p21 INHIBITORS |
| WO2008076857A2 (en) * | 2006-12-14 | 2008-06-26 | Wisconsin Alumni Research Foundation | Method and compositions for inhibiting mage protein interaction with kap-1 |
| US20120190735A1 (en) * | 2009-09-10 | 2012-07-26 | E-Therapeutics Plc | Cancer Cell Apoptosis |
| US20140199233A1 (en) * | 2011-05-11 | 2014-07-17 | The Regents Of The University Of California | Enhanced Growth Inhibition of Osteosarcoma by Cytotoxic Polymerized Liposomal Nanoparticles Targeting the Alcam Cell Surface Receptor |
| CN106794125A (en) * | 2014-04-03 | 2017-05-31 | 剑桥企业有限公司 | For treating or preventing lamin sick, aging and cancer NAT10 conditioning agents |
| CN110951873A (en) * | 2019-12-03 | 2020-04-03 | 中山大学 | Bone and sarcoma marker, application thereof and kit |
| CN111424082A (en) * | 2019-01-09 | 2020-07-17 | 上海中医药大学附属龙华医院 | Application of lncRNA-SNHG6 gene in preparation of medicine for treating osteosarcoma |
| WO2020257401A1 (en) * | 2019-06-21 | 2020-12-24 | The Children's Medical Center Corporation | Methods and compositions for the treatment of cancer |
| WO2021232094A1 (en) * | 2020-05-19 | 2021-11-25 | Hudson Institute of Medical Research | Hedgehog signaling -dependent cancer treatment |
-
2023
- 2023-08-09 CN CN202310995413.7A patent/CN116726181B/en active Active
Patent Citations (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003020930A1 (en) * | 2001-08-29 | 2003-03-13 | The Board Of Trustees Of The University Of Illinois | IDENTIFICATION AND USE OF MAMMALIAN p21 INHIBITORS |
| WO2008076857A2 (en) * | 2006-12-14 | 2008-06-26 | Wisconsin Alumni Research Foundation | Method and compositions for inhibiting mage protein interaction with kap-1 |
| US20120190735A1 (en) * | 2009-09-10 | 2012-07-26 | E-Therapeutics Plc | Cancer Cell Apoptosis |
| US20140199233A1 (en) * | 2011-05-11 | 2014-07-17 | The Regents Of The University Of California | Enhanced Growth Inhibition of Osteosarcoma by Cytotoxic Polymerized Liposomal Nanoparticles Targeting the Alcam Cell Surface Receptor |
| CN106794125A (en) * | 2014-04-03 | 2017-05-31 | 剑桥企业有限公司 | For treating or preventing lamin sick, aging and cancer NAT10 conditioning agents |
| CN111424082A (en) * | 2019-01-09 | 2020-07-17 | 上海中医药大学附属龙华医院 | Application of lncRNA-SNHG6 gene in preparation of medicine for treating osteosarcoma |
| WO2020257401A1 (en) * | 2019-06-21 | 2020-12-24 | The Children's Medical Center Corporation | Methods and compositions for the treatment of cancer |
| CN114269920A (en) * | 2019-06-21 | 2022-04-01 | 儿童医疗中心有限公司 | Methods and compositions for treating cancer |
| CN110951873A (en) * | 2019-12-03 | 2020-04-03 | 中山大学 | Bone and sarcoma marker, application thereof and kit |
| WO2021232094A1 (en) * | 2020-05-19 | 2021-11-25 | Hudson Institute of Medical Research | Hedgehog signaling -dependent cancer treatment |
Non-Patent Citations (2)
| Title |
|---|
| IAIN SCOTT 等: "Identification of a molecular component of the mitochondrial acetyltransferase programme: a novel role for GCN5L1", BIOCHEM. J., vol. 443, no. 3, pages 657 * |
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| CN116726181B (en) | 2023-10-20 |
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