CN109536498B - A kind of PABPC5 gene inhibitor and use thereof - Google Patents
A kind of PABPC5 gene inhibitor and use thereof Download PDFInfo
- Publication number
- CN109536498B CN109536498B CN201811503752.4A CN201811503752A CN109536498B CN 109536498 B CN109536498 B CN 109536498B CN 201811503752 A CN201811503752 A CN 201811503752A CN 109536498 B CN109536498 B CN 109536498B
- Authority
- CN
- China
- Prior art keywords
- pabpc5
- glioma
- gene
- inhibitor
- cells
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
-
- 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
- A61K31/711—Natural deoxyribonucleic acids, i.e. containing only 2'-deoxyriboses attached to adenine, guanine, cytosine or thymine 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
- A61P35/00—Antineoplastic agents
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Genetics & Genomics (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Molecular Biology (AREA)
- Biomedical Technology (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biochemistry (AREA)
- Zoology (AREA)
- Biotechnology (AREA)
- General Engineering & Computer Science (AREA)
- Wood Science & Technology (AREA)
- Epidemiology (AREA)
- Microbiology (AREA)
- Plant Pathology (AREA)
- Biophysics (AREA)
- Physics & Mathematics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Abstract
本发明属于生物医药领域，具体涉及一种PABPC5基因抑制剂及其在抗胶质瘤中的用途。所述的PABPC5基因靶向抑制剂的基因序列为5’‑GGAACATTCTGTCCTGCAAAG‑3’（SEQ ID No.1），与SEQ ID No.1所示的DNA序列具有90%同源性且具有相同或相近功能的DNA序列。PABPC5基因抑制剂用于制备抗肿瘤药物中的用途，所述肿瘤为脑胶质瘤。通过其在脑胶质瘤中的应用，可以抑制胶质瘤细胞的迁移和侵袭，诱导胶质瘤细胞凋亡，具有针对性的预防和提高胶质瘤治疗效果的优点。
The invention belongs to the field of biomedicine, and in particular relates to a PABPC5 gene inhibitor and its use in anti-glioma. The gene sequence of the PABPC5 gene targeting inhibitor is 5'-GGAACATTCTGTCCTGCAAAG-3' (SEQ ID No.1), which has 90% homology and is identical or similar to the DNA sequence shown in SEQ ID No.1 functional DNA sequences. Use of a PABPC5 gene inhibitor for preparing an antitumor drug, wherein the tumor is glioma. Through its application in glioma, the migration and invasion of glioma cells can be inhibited, and the apoptosis of glioma cells can be induced, which has the advantages of targeted prevention and improvement of the therapeutic effect of glioma.
Description
Technical Field
The invention belongs to the field of biological medicines, and particularly relates to an inhibitor of PABPC5 gene and application thereof in resisting glioma.
Background
Glioblastoma is the most common and most malignant tumor of the central system. At present, the treatment means mainly comprises operation and radiotherapy and chemotherapy as auxiliary treatment. However, since glioblastoma has biological characteristics such as highly invasive growth and vigorous angiogenesis, the recurrence of the operation is inevitable even when the operation is performed under imaging and microscopic resection. After comprehensive treatment, the survival period of the median is still not more than 15 months, and the 5-year survival rate is not more than 15%. In recent years, with the continuous and deep research of gene molecule level, the medical community at home and abroad has new understanding and comprehension of the pathogenesis of glioma, more and more specific genes closely related to the occurrence and development of glioma are discovered, and a large number of clinical researches show that the expression of the specific genes is closely related to the effectiveness of chemotherapeutic drugs. Therefore, the specific gene of the glioma is determined, the expression state of the gene is determined, and a medicinal preparation is developed and developed aiming at the gene, so that the treatment efficiency of the glioma can be effectively improved, the toxic and side effects of the medicament are reduced, and the method has a very wide application prospect.
PABPC5 (Poly (A) binding protein cytoplasmic 5), an RNA binding protein that binds to the poly (A) tail. PABPC5 is located at xq21.31 and contains 2 exons. There are studies reporting the detection of PABPC5 expression in adult brains, and there are also studies indicating that PABPC5 is closely associated with the formation of sex chromosomes. The expression of PABPC5 in malignant brain glioma and the regulation of glioma cell biological behavior are not discovered at present. In the early stage, the expression level of PABPC5 was detected by real-time PCR. The result shows that the expression level of the PABPC5 in the brain glial cells is obviously higher than that of the normal astrocyte group, and the result indicates that the PABPC5 is possibly involved in the functional regulation of the occurrence and the development of glioma.
The principle of RNA interference technology is the process of utilizing Dicer enzyme to cut RNA molecules, forming an RNA silencing complex, combining target RNA molecules in a targeted mode and further degrading the RNA molecules. The invention utilizes RNA interference technology to develop TSNAX gene inhibitor, which plays a role in glioma gene therapy field.
At present, the role and the related mechanism of the PABPC5 in the development of glioma are not reported, and the application of the PABPC5 in the aspect of glioma gene therapy is still a blank. Therefore, the development of a PABPC 5-related drug is a problem to be solved. The implementation of the invention can realize the conversion of the theoretical research of the pathogenesis of glioma to clinical application, solve the problems of glioma recurrence and treatment resistance and effectively improve the treatment effect of glioma.
Disclosure of Invention
In view of the defects in the prior art, the invention provides a specific gene inhibitor with high expression in glioma, and the application of the specific gene inhibitor in glioma can inhibit the migration and invasion of glioma cells, induce the apoptosis of glioma cells and have the advantages of preventing and improving the treatment effect of glioma in a targeted manner.
In order to achieve the above object, the present invention adopts the following technical solutions.
A gene sequence of the targeted inhibitor of the PABPC5 gene is 5'-GGAACATTCTGTCCTGCAAAG-3' (SEQ ID No.1) or a DNA sequence which has 90 percent of homology with the DNA sequence shown in the SEQ ID No.1 and has the same or similar functions.
The target inhibitor of the PABPC5 gene can inhibit an shRNA sequence expressed by the PABPC5 gene, the shRNA template sequence comprises a sense strand and an antisense strand, and the sense strand and the antisense strand are respectively.
The sense strand.
5’-CACCGGAACATTCTGTCCTGCAAAGTTCAAGAGACTTTGCAGGACAGAATGTTCCTTTTTTG-3’（SEQ ID No.2）。
The antisense strand.
5’-GATCCAAAAAAGGAACATTCTGTCCTGCAAAGTCTCTTGAAGGAACATTCTGTCCTGCAAAG-3’（SEQ ID No.3）。
A transcription product for transcribing the shRNA, which has the sequence.
5’-GGAACATTCTGTCCTGCAAAGTTCAAGAGAGGAACATTCTGTCCTGCAAAG-3’（SEQ ID No.4）。
The application of an inhibitor of the PABPC5 gene in preparing an anti-tumor medicament, wherein the tumor is brain glioma.
The anti-tumor medicine is a pharmaceutical composition which comprises a therapeutic amount of an inhibitor of PABPC5 gene and a pharmaceutical carrier or excipient.
The anti-tumor medicament is a pharmaceutically acceptable dosage form, preferably an injection.
Compared with the prior art, the invention has the beneficial effects.
1) The RNA binding protein can maintain the dryness of tumor stem cells, and participate in the generation, development, metastasis and angiogenesis of tumors by enhancing the stability of tumor-associated RNA, so that chemotherapeutic drugs have drug resistance. Therefore, the RNA binding protein can play the role of oncogene through a plurality of mechanisms, promote the tumorigenesis and development and inhibit the treatment effect. The PABPC5 is a RNA binding protein with high specificity and expression for brain glioma, and can promote the generation and development of tumor and induce drug resistance. Mainly aims at the PABPC5 gene with high specificity expression of the brain glioma, achieves the target treatment and reduces the side effect.
2) The inhibitors of the invention are characterized by any pharmacotherapeutically acceptable dosage form, and have great clinical utility values.
3) The research and development of inhibitors aiming at tumor cell specific high expression molecules are main targets of the research and development of current tumor treatment drugs, but the development of tumor targeted drugs is restricted due to long drug research and development period, poor treatment effect and the like. The RNA interference technology has the characteristics of safety and reliability, delivery of related tumor treatment drugs through various ways outside and inside cells, and the like, and provides a relatively quick and revolutionary tumor drug research and development way for tumor treatment.
4) The invention applies RNA interference technology to prepare the RNA binding protein PABPC5 gene inhibitor, has the characteristics of targeted therapy, safety and effectiveness, relatively quick production and long-term effectiveness, and fills the defects in the research and development of anti-tumor drugs.
Drawings
FIG. 1 shows the Real-time PCR method for detecting the expression of PABPC5 in normal brain tissue specimens and glioma tissue specimens. Compared with the normal brain tissue specimen, the expression of the PABPC5 in the glioma tissue is obviously increased, and the difference has statistical significance (n =5,** P<0.01 vs. normal brain tissue); compared with low-grade glioma specimens, the expression of the PABPC5 in glioblastoma multiforme tissues is obviously increased, and the difference has statistical significance. (n = 5) of the total number of the units,## P<low grade glioma at 0.01 vs).
FIG. 2 is the Real-time PCR method for detecting the expression of PABPC5 in human brain glioma U87 and U251 cells after the PABPC5 gene inhibitor is applied. In U87 and U251 cells, PABPC5 was in the inhibitor group compared to the blank control groupThe expression is obviously reduced, and the difference has statistical significance. (n = 3) of the total number of the units,** P<0.01 vs. blank).
FIG. 3 shows the change of cell migration ability of human brain glioma U87 and U251 after applying PABPC5 gene inhibitor in Transwell assay. (n = 3) of the total number of the units,** P<0.01 vs. blank).
FIG. 4 shows the change of invasion capacity of human brain glioma cells U87 and U251 after the Transwell test by using PABPC5 gene inhibitor. (n = 3) of the total number of the units,** P<0.01 vs. blank).
FIG. 5 shows the change of human brain glioma U87 cell apoptosis ability after the PABPC5 gene inhibitor is applied through flow cytometry.
Detailed Description
The following describes the preparation of the antitumor substance of the present invention in detail with reference to the accompanying drawings and examples.
1. Real-time quantitative PCR detected the expression of PABPC 5.
1.1 Trizol method to extract total RNA from tissues and cells.
1.1.1 washing the collected cells with cold PBS (frozen tissue in liquid nitrogen is crushed at 0 ℃ for 30 seconds using a tissue homogenizer at 5000 rpm), adding 1 ml Trizol reagent and beating several times, observing the cells under the microscope to form oil drops (fully lysed), then transferring into a 1.5ml EP tube, standing for 5 minutes to fully lyse them.
1.1.2 to the sample was added 0.2 ml of chloroform, and allowed to stand at room temperature for 3 minutes with vigorous shaking manually.
1.1.3 centrifugation at 12000g at 4 ℃ for 15 minutes, taking the upper aqueous phase into a new EP tube, adding 0.5 ml of isopropanol, mixing by turning upside down, and standing at room temperature for 10 minutes.
1.1.44 deg.C, 12000g, centrifuging for 15 minutes, discarding the supernatant, and adding 1 ml 75% ethanol.
7500g at 1.1.54 deg.C, centrifuging for 5 minutes, drying at room temperature for 15 minutes, adding 40 μ l DEPC water, and freezing the sample in a refrigerator at-80 deg.C.
1.2 one-step dye method qRT-PCR detects the expression of PABPC 5.
Total RNA extraction using Trizol: trizol was applied directly to the cells and blown. After leaving at room temperature for 5 minutes, 0.2 ml of chloroform was added to the tube, followed by vigorous shaking for 15 seconds, and left at room temperature for 2 to 3 minutes. Centrifuge at 12000g for 15 min at 4 ℃ and take the upper aqueous phase to another new tube. 0.5 ml of isopropanol was added thereto, and the mixture was left at room temperature for 5 minutes with shaking. Centrifuge at 12000g for 10 min at 4 deg.C, discard the supernatant, wash the tube bottom white precipitate with 1 ml 75% ethanol, and vortex. Centrifuging at 4 deg.C for 5 min at 7500g, discarding the supernatant, and placing the EP tube upside down on clean filter paper until ethanol is completely volatilized. Adding appropriate amount of DEPC water, and slightly beating until RNA is completely dissolved. Total RNA was analyzed by Nanodrop spectrophotometer to determine RNA concentration and OD260/OD280 ratio, which confirmed purity (RNA purity validation standard: RNA purity was very high when OD260/OD280 was 1.7-2.0, protein or phenol contamination was indicated when OD260/OD280 was < 1.7, and isothiocyanate residual was indicated when OD260/OD280 was > 2.0).
Applying One Step SYBR® PrimeScript®PLUS RT-PCR Kit (TaKaRa, China), according to the instructions for amplification. The main steps comprise that after the synthesized target gene and GAPDH upstream and downstream primers are dissolved by 0.1 percent DEPC water, an RT-PCR reaction system (20 mu l) is prepared: one Step SYBR buffer, 10 mul; TaKaRa Ex Taq HS Mis, 1.2 μ l; PrimeScript PLUS TRase Mix, 0.4. mu.l; PCR upstream primer, 0.8. mu.l; PCR downstream primer, 0.8. mu.l; ROX reference Dye, 0.4. mu.l; total RNA, 2 μ l; RNase Free dH2O, 4.4. mu.l. Mixing the above components, labeling, and placing into gene amplification instrument. The conditions and parameters for amplification were: 42 ℃, 5 min, 95 ℃, 10 s; 40 cycles of 95 ℃ 5s and 60 ℃ 34 s. CT values were determined with GAPDH as internal reference and 2-△△Ct represents the relative expression level of PABPC 5.
Detecting the expression level of the PABPC5 gene in normal astrocytes and glioma cells, as shown in FIG. 1, the expression of PABPC5 in glioblastoma tissues is significantly increased compared with that in normal brain tissue specimens, and the expression level is increased along with the increase of tumor grade.
2. Preparation and application of PABPC5 gene inhibitor.
The interfering sequence of the PABPC5 gene was designed, and the target gene sequence targeting the human PABPC5 gene and specifically inhibiting the expression of the PABPC5 gene was selected as follows.
5’-GGAACATTCTGTCCTGCAAAG-3’（SEQ ID No.1）。
The GGAACATTCTGTCCTGCAAAG sequence is input in the homologous sequence alignment analysis nucleotide blast of NCBI for alignment analysis, and the result shows that the sequence has no high homology with other human mRNA genes and can be used as a specific sequence for specifically interfering the PABPC5 gene.
The shRNA sequence which targets the human PABPC5 gene and inhibits the expression of the PABPC5 gene is designed aiming at the target sequence as follows, and comprises a sense strand and an antisense strand, and the shRNA sequence is shown in the specification.
The sense strand.
5’-CACCGGAACATTCTGTCCTGCAAAGTTCAAGAGACTTTGCAGGACAGAATGTTCCTTTTTTG-3’（SEQ ID No.2）。
The antisense strand.
5’-GATCCAAAAAAGGAACATTCTGTCCTGCAAAGTCTCTTGAAGGAACATTCTGTCCTGCAAAG-3’（SEQ ID No.3）。
The sequence of the transcription product of the shRNA is shown in the specification.
5’-GGAACATTCTGTCCTGCAAAGTTCAAGAGAGGAACATTCTGTCCTGCAAAG-3’ （SEQ ID No.4）。
The above sequence information was designed and synthesized into corresponding plasmids as PABPC5 gene inhibitors. PABPC5 gene inhibitor transfection: plasmids U6/GFP/Neo of sh-NC and sh-PABPC5 silence the expression of PABPC5, and empty plasmids without PABPC5 sequence or shRNA are used as experimental negative controls; culturing glioma cells by using a 24-hole culture plate, and performing transfection when the cell growth reaches about 80%; plasmid, Opti-MEM, required for the preparation of transfections®I and LTX and Plus reagent (Life Technologies) transfection reagents. Tube A: one well was dissolved with 1. mu.g plasmid DNA in 50. mu.l of Opti-MEM I + 1. mu. l p3000 for 5 min, tube B: the wells were dissolved in 50. mu.l of Opti-MEM according to 1. mu.l of LTX and Plus®In the step I; evenly mixing A, B two tubes, and standing for 5 min; sucking out the culture solution, adding 100 muL of transfection mixed solution into each hole, and adding 400 muL of EBM-2 culture solution; after 48 h, the selection is carried out with medium containing the antibiotic G418 at a concentration of 0.4 mg/mL, with increasing G418Concentration, approximately 4 weeks later, resulted in a cell line capable of stably silencing PABPC 5. In subsequent experiments, the groups were divided into 3 groups, each of which was: normal group, blank control group transfected with PABPC5 silencing empty plasmid, inhibitor group transfected with PABPC5 silencing plasmid.
And detecting the expression of the PABPC5 in U87 and U251 glioma cells after applying the PABPC5 gene inhibitor. The results are shown in fig. 2, where PABPC5 was significantly down-regulated in the inhibitor group compared to the blank control group.
3. Cell Transwell migration and invasion experiments.
1) 500 μ l of DMEM high-glucose culture solution containing 10% serum is added into each hole of a 24-hole cell culture plate, and transwell chambers with the aperture of 8 μm are placed in the holes.
2) After cell counting, different groups of cells are blown into cell suspension by DMEM high-sugar culture solution without serum, the cell suspension is respectively and uniformly spread in the upper chamber, and 100 mu l of cell suspension is added into each small chamber, and approximately 10000 cells are contained. The mixture was incubated in a 37 ℃ incubator for 24 hours.
3) After 24 hours, the chamber was taken out, and the cells that did not migrate on the inner surface of the upper chamber were wiped off with a cotton swab, and a fixing solution was prepared at a ratio of methanol/glacial acetic acid = 3: 1.
4) The chamber was placed in a fixative solution and the cells on the bottom of the chamber were fixed for 30 minutes.
5) The chamber was washed with PBS and then dried. Preparing a Giemsa dye solution: the ratio of the working solution is 1: 9. Giemsa was stained with the drop on the bottom of the chamber for 1 hour.
6) The cells were washed twice with PBS, observed to migrate under an inverted 400 Xmicroscope, and counted by randomly taking 5 fields of each group of cells to represent the migration ability of the cells.
4. Cell Transwell invasion assay.
1) Uniformly paving 50 mul of Matrigel matrix with the concentration of 500 ng/mul on the inner surface of the small chamber, and putting the Matrigel matrix into a 37 ℃ thermostat for 4 hours to solidify the Matrigel.
2) Then, the cell suspension was applied again in the same manner as the migration experiment.
As shown in fig. 3 and 4, after the PABPC5 gene inhibitor is applied, the glioma U87 and U251 cell migration and invasion capacities of the inhibitor group are significantly reduced compared with those of the blank control group.
5. And (3) carrying out an apoptosis experiment.
1) Cells were washed twice with pre-chilled PBS. The cells were digested with trypsin without EDTA, gently blown into a cell suspension, transferred to a 1.5ml centrifuge tube, and centrifuged at 1000rpm for 3 minutes to collect the cells.
2) Washing was continued with PBS, centrifugation was carried out at 1000rpm for 3 minutes, and after centrifugation, the supernatant was decanted and repeated twice.
3) The working solution was diluted 10 × binding buffer ten times. 100 mul Binding Buffer was added to each tube to suspend the cells.
4) 5 mul Annexin V-PI and 5 mul FITC were added to each tube in succession and mixed well in the dark for 15 minutes at room temperature.
5) Before loading, 400 μ l of 1 × binding buffer was added to each tube, and after blowing uniformly, the change of apoptosis was detected by an up-flow cytometer (FACScan, BD Co., USA).
As shown in fig. 5, compared with the blank control group, the PABPC5 gene inhibitor can significantly induce the apoptosis of glioma U87 cells.
SEQUENCE LISTING
<110> university of Chinese medical science
<120> PABPC5 gene inhibitor and application thereof
<130> 4
<160> 4
<170> PatentIn version 3.3
<210> 1
<211> 21
<212> DNA
<213> Artificial sequence
<400> 1
ggaacattct gtcctgcaaa g 21
<210> 2
<211> 62
<212> DNA
<213> Artificial sequence
<400> 2
caccggaaca ttctgtcctg caaagttcaa gagactttgc aggacagaat gttccttttt 60
tg 62
<210> 3
<211> 62
<212> DNA
<213> Artificial sequence
<400> 3
gatccaaaaa aggaacattc tgtcctgcaa agtctcttga aggaacattc tgtcctgcaa 60
ag 62
<210> 4
<211> 53
<212> DNA
<213> Artificial sequence
<400> 4
ggaacattct gtcctgcaaa gttcaagaga ggaacattct gtcctgcaaa g 51
Claims (1)
1. The application of the PABPC5 gene targeted inhibitor in preparing anti-glioma drugs is characterized in that the PABPC5 gene targeted inhibitor is an shRNA sequence capable of inhibiting the expression of the PABPC5 gene, and the target sequence of the shRNA sequence is 5'-GGAACATTCTGTCCTGCAAAG-3' (SEQ ID No. 1).
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811503752.4A CN109536498B (en) | 2018-12-10 | 2018-12-10 | A kind of PABPC5 gene inhibitor and use thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811503752.4A CN109536498B (en) | 2018-12-10 | 2018-12-10 | A kind of PABPC5 gene inhibitor and use thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN109536498A CN109536498A (en) | 2019-03-29 |
| CN109536498B true CN109536498B (en) | 2021-06-29 |
Family
ID=65853309
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201811503752.4A Expired - Fee Related CN109536498B (en) | 2018-12-10 | 2018-12-10 | A kind of PABPC5 gene inhibitor and use thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN109536498B (en) |
-
2018
- 2018-12-10 CN CN201811503752.4A patent/CN109536498B/en not_active Expired - Fee Related
Non-Patent Citations (3)
| Title |
|---|
| A novel poly(A)-binding protein gene (PABPC5) maps to an X-specific subinterval in the Xq21.3/Yp11.2 homology block of the human sex chromosomes;P Blanco等;《Genomics》;20010515;第74卷(第1期);第1-11页 * |
| Homo sapiens poly(A) binding protein cytoplasmic 5 (PABPC5), mRNA，NM_080832.3;Lyons PA等;《NCBI GenBank》;20181124;第1-3页 * |
| The PABPC5/HCG15/ZNF331 Feedback Loop Regulates Vasculogenic Mimicry of Glioma via STAU1-Mediated mRNA Decay;Fangkun Jing等;《Mol Ther Oncolytics》;20200626;第17卷;第216-231页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN109536498A (en) | 2019-03-29 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Yang et al. | Breast cancer-derived exosomes regulate cell invasion and metastasis in breast cancer via miR-146a to activate cancer associated fibroblasts in tumor microenvironment | |
| He et al. | MicroRNA-181a suppresses salivary adenoid cystic carcinoma metastasis by targeting MAPK–Snai2 pathway | |
| Chen et al. | Knockdown of TRIM47 inhibits glioma cell proliferation, migration and invasion through the inactivation of Wnt/β-catenin pathway | |
| CN107164528B (en) | Application of non-coding gene related to liver cancer occurrence and development | |
| Li et al. | The effect of miR-21 on SWOZ2 glioma cells and its biological mechanism | |
| CN107523566B (en) | Targeting inhibitor of MCM3AP-AS1 gene and application thereof | |
| CN108220446B (en) | Application of LINC01356 as molecular marker in gastric cancer | |
| CN112716946B (en) | Application of sultam-cyclohexanone spiro derivative 1-3-51 in preparation of medicine for treating gastric cancer | |
| CN109536498B (en) | A kind of PABPC5 gene inhibitor and use thereof | |
| CN112921039A (en) | Application of small molecular RNA hsa-miR-451a in preparation of medicine for treating cerebral arterial thrombosis | |
| CN119351402A (en) | RNA for treating triple-negative breast cancer and its application | |
| CN109554364B (en) | TSNAX gene inhibitor and application thereof in tumors | |
| CN107753956B (en) | A kind of targeted inhibitor of RAX2 gene and use thereof | |
| CN115998756A (en) | Application of si-PTBP1 in preparation of medicine for improving cancer cell chemotherapy sensitivity, medicine preparation and detection method | |
| CN110157708A (en) | A kind of inhibitor targeting linc01023 gene for inhibiting human brain glioma and its application | |
| CN111172289B (en) | Marker of miRNA for diagnosing and treating liver cancer | |
| CN110946873B (en) | Application of microRNA-29a-3p as a target for the prevention and treatment of glioma vascular mimicry | |
| CN110607368B (en) | Application of miRNA3926-1 gene as a diagnostic and therapeutic marker of pancreatic cancer | |
| CN107723367A (en) | Application of miRNA-885-3p and product using same | |
| CN108034719A (en) | The application of GINS4 genes or GINS4 albumen as biomarker in the pre- diagnostic reagent for preparing adenocarcinoma of lung | |
| CN113855663A (en) | Use of Rubescensine A in the preparation of anti-prostate cancer drugs | |
| CN107184983B (en) | A target for diagnosis and treatment of lung adenocarcinoma | |
| CN107641625B (en) | MTF1 gene targeted inhibitor and application thereof | |
| CN111534516B (en) | Target inhibitor of SNORD83A gene and application thereof | |
| CN112280859B (en) | Breast cancer marker and application thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20210629 |
|
| CF01 | Termination of patent right due to non-payment of annual fee |