CN112210600B - Application and detection method of circRNA0003307 gene - Google Patents
Application and detection method of circRNA0003307 gene Download PDFInfo
- Publication number
- CN112210600B CN112210600B CN202011274191.2A CN202011274191A CN112210600B CN 112210600 B CN112210600 B CN 112210600B CN 202011274191 A CN202011274191 A CN 202011274191A CN 112210600 B CN112210600 B CN 112210600B
- Authority
- CN
- China
- Prior art keywords
- preparation
- gene
- expression
- patients
- application
- 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.)
- Active
Links
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
- C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/158—Expression markers
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/178—Oligonucleotides characterized by their use miRNA, siRNA or ncRNA
Abstract
An application of circRNA0003307 gene and a detection method thereof, belonging to the technical field of rheumatism molecular biology. The preparation for detecting the circRNA0003307 gene expression quantity comprises a primer pair with nucleotide sequences shown as SEQ ID NO.1 and NO.2, and the preparation for detecting the gene expression quantity can be applied to preparation of a ankylosing spondylitis detection preparation. The specific interference sequence si-circRNA0003307 can obviously inhibit the expression level of circRNA0003307 in synovial cells, and can lead to the obvious weakening of the multiplication capacity of the synovial cells compared with the prior art, the reduction of inflammatory cytokine production induced by LPS, and the obvious reduction of phosphorylation and nuclear translocation of PI3K and AKT. The discovery is expected to further enrich and improve the research of AS pathogenesis and bring hope for developing novel biomarkers for AS early diagnosis, targeted therapy and prognosis evaluation.
Description
Technical Field
The invention belongs to the technical field of rheumatism molecular biology, and relates to the fields of expression, application and detection of a circular RNA key gene (circRNA0003307), in particular to application and a detection method of a circRNA0003307 gene.
Background
Ankylosing Spondylitis (AS) is a common inflammatory Rheumatic disease that affects The medial axis skeleton, causing characteristic inflammatory back pain, which may lead to structural and functional impairment and a decrease in quality of life (Jurgen Branu, Sieber J. The Lancet,2007,369(9570): 1379. 1390.), often accompanied by systemic pathologies such AS uveitis, valvular lesions of The heart, lungs, intestines (Smith JA. Update on spinal cord pathology. Current Allergy & Association. 20115 (1): 489; Ciccia F, Guignino G, Rizzo A, real bone disease. dynamics & relating to diagnosis J. 11276. The root canal of Diseases). The incidence of AS in chinese populations is similar to that of white european population, about 0.24%. About 4% of patients lose partial labor 5 years after The onset of AS, and about 50% after 45 years (Pedersen Susanne Juhl, Maksymych Filter P, The Pathogenesis of unhealthy sports: an Update [ J ] Current rheumology reports, 2019,21: 58). The pathogenesis of AS is still unclear and may be related to genetics, infection, environment, immunity, etc. The key to the treatment is to relieve the inflammatory symptoms of AS patients AS soon AS possible, relieve pain, control disease activities, delay the progress of diseases and reduce teratogenic and disabling injuries of the patients caused by the diseases. However, the current therapeutic drugs for AS include non-steroidal anti-inflammatory drugs, immunosuppressants, antirheumatic drugs, glucocorticoids and the like for improving disease conditions, have large side effects after long-term administration, cause intolerance, and have adverse reactions such AS the liver and kidney functions of the gastrointestinal tract affected, and cause heavy physical and psychological burdens on patients (Hasikova Lenka, Pavlikova Marketa, Hulejova Hana et al. Serum uric acid implants in patients with systemic auto immune diseases after 3 patients of clinical diagnosis with TNF inhibitors [ J ] Rheumatous. int.,2019,39: 1759-.
Circular RNAs (CircRNAs) are a novel class of endogenous non-coding RNAs with covalently closed Circular structures (R. Ashwal-Fluss, M. Meyer, N.R. Pamulti et al, Circular RNA biogenesis protocols with pre-mRNA partitioning, molecular cell, 2014.55-66.; S.Memczak, M.Jens, A.Elefinitrietal, Circular RNA of large class of RNAs with regulatory pores, Nature,2013, 333, 495, 338.). Unlike linear RNA, CircRNA has no free 3 'Polya tail and 5' end cap, which prevents their digestion by exonucleases. Thus, the closed loop structure of circrnas makes them very stable and potentially useful as molecular markers. CircRNAs have been designated as potential regulators of micrornas (mirnas), RNA binding proteins (RPBs), and linear protein-encoded transcripts. (Salzman Julia, Gawad Charles, Wang Peter Lincoln et al. circular RNAs are from loops of human genes in reverse cell types. [ J ]. PLoS One,2012,7: e 30733; Luo Qing, Zhang Lu, Fang Le et al. circular RNAs hsa _ circ _0000479in intrinsic magnetic sponge cells as non-genomic pairs for system nucleic acid residues. [ J ]. autoimmmunity, miRNA 2020,53: 167: 176.) circular RNAs can regulate expression of proteins as miRNA sponges, regulate expression of their parent genes by cis or trans, and participate in translation of proteins. In addition, the circRNAs play an important role in the generation and development processes of immunity and related diseases, and are expected to become molecular markers for disease diagnosis. (human TB, Wiklund ED, Bramsen JB, et al. incorporated gene cloning. of A circulating antisense RNA. EMBO J.2011; 30: 4414. sub.4422.; Abe N, Matsumoto K, Nishihara M, et al. Rolling circulation transformation of circulating RNA in circulating cells. Sci. repeat. 2015; 5:16435.Li H, Li K, Lai W, et al.; composite circulating RNA profiles in membranes of nucleic acids in kinetic proteins. dye copolymers systems for use in microorganisms systems for expression vectors, library 27. sub.8. library 27, library 27. sub.27. 11. library 27. sub.11. library 27. Miq.7. sub.11. micro vector miR-11. miR-7, miR-11. miR-Miq. 7. Miq. 7. Miq. variants, Miq. variants of nucleic acids of proteins, 2018: 1-20; qian B P, Ji M L, Qia Y, et al.identification of Serum miR-146a and miR-155as Novel nonlinear composite Biomarkers for alkylosing sponge [ J ]. Spine,2016,41(9): 735-. Furthermore, previous studies have shown that abnormal expression of a number of lncRNAs is also observed in peripheral blood of AS patients. However, research on CircRNA in AS patients is currently less. (Kou J, Liu G, Liu X, et al. profiling and Bioinformatics Analysis of differential Expressed cyclic RNAs in Spinal fluid Tissues of Patients with analytical Properties and separations International,2020 (1):1-12.)
Disclosure of Invention
Aiming at the current situation that the existing AS treatment medicine lacks targeting and pertinence and has large side effect after long-term administration, the invention firstly provides the application of a circular RNA key gene circRNA0003307 in the preparation of an Ankylosing Spondylitis (AS) detection preparation and a ankylosing spondylitis prognosis evaluation preparation.
The technical scheme adopted by the invention is as follows: an application of a preparation for detecting the circRNA0003307 gene expression quantity in preparing a ankylosing spondylitis detection preparation, wherein the preparation for detecting the circRNA0003307 gene expression quantity comprises a primer pair with a nucleotide sequence shown as SEQ ID No.1 and SEQ ID No. 2.
Secondly, the preparation for detecting the expression level of the circRNA0003307 gene further comprises: 10ul 2 XSSYBR Premix Ex Taq II, 1.6ul 50 XROX Reference Dye, 2ul cDNA (2.5ng/ul), 1ul each of SEQ ID NO.1 and SEQ ID NO.2 at a concentration of 10umol/L, ddH2O is complemented to 20 ul.
Thirdly, the invention also provides a detection method of the circRNA0003307 gene, which comprises the steps of peripheral blood mononuclear cell extraction, total RNA extraction by a TRIzol method, determination of RNA concentration and purity, cDNA synthesis and PCR amplification.
Fourthly, the invention also provides application of the circRNA0003307 gene in preparation of targeted therapeutic preparations for ankylosing spondylitis, and particularly provides application of the circRNA0003307 gene in preparation of specific interference sequences for interfering the circRNA0003307 gene in cells.
Fifth, the invention provides a targeted therapeutic preparation for ankylosing spondylitis, which comprises a specific interference sequence si-circRNA0003307, and the nucleotide sequence of the targeted therapeutic preparation is shown as SEQ ID No. 3. The specific interference sequence si-circRNA0003307 is designed and synthesized aiming at the full-length sequence of the circRNA0003307, and can be used for infecting synovial fibroblasts to enable the circRNA0003307 gene to interfere in the cells.
The beneficial effects of the invention are as follows:
the specific interference sequence si-circRNA0003307 of the invention can obviously inhibit the expression level of circRNA0003307 in synovial cells, and can lead the multiplication capacity of the synovial cells to be obviously weakened compared with the prior art, inflammatory cytokine production induced by LPS is reduced, and phosphorylation and nuclear translocation of PI3K and AKT are obviously reduced.
The invention systematically explores the expression of circRNA0003307 gene and related protein in AS, and the example research proves that: compared with a healthy control group, the expression of the circRNA0003307 in the peripheral blood mononuclear cells of the AS patients is obviously increased, and the expression is in positive correlation with the disease activity index. circRNA0003307 interference vector significantly inhibited the inflammatory response of synovial cells. The application discovers and verifies the expression and the function of circRNA0003307 in AS. The discovery is expected to further enrich and improve the research of AS pathogenesis and bring hope for developing novel biomarkers for AS early diagnosis, targeted therapy and prognosis evaluation.
Drawings
FIG. 1 is a diagram showing the expression of the cricRNA0003307 gene in AS patients and healthy control groups.
FIG. 2 is a graph showing the correlation between cricRNA0003307 expression and ESR and CRP in AS patients.
FIG. 3 is a diagram showing the expression of the interference and overexpression group of cricRNA0003307 in the synovial cells of hip joints of AS patients.
FIG. 4 is a schematic representation of the inhibition of inflammatory cytokine production by cricRNA0003307 interference.
FIG. 5 is a schematic diagram of interference inhibition of PI3K, AKT phosphorylation and nuclear translocation by cricRNA 0003307.
Detailed Description
The following examples are examples of experimental methods in which specific conditions are not specified, and the tests are usually carried out under conventional conditions or under conditions recommended by the manufacturers.
Example 1
To investigate the expression of circRNA0003307 and the expression of regulatory proteins (PI3K, AKT, TNFAIP2 and IL-1. beta.) in peripheral blood mononuclear cells of AS patients.
After the project is examined by ethics committee, the applicant systematically studies new diagnosis and treatment targets of human AS, extracts PBMCs by extracting peripheral blood of AS patients, and detects the expression of circRNA0003307 gene by a real-time PCR method.
In the present example, 30 blood samples of patients in AS active period were collected, and 30 blood samples of healthy persons in control group were collected, and 60 samples were collected (the specific information of 30 patients is shown in Table 1, and the characteristics of the samples are shown in Table 2).
TABLE 1 sample information
TABLE 2 sample characterization
In this example, 30 AS and 30 healthy control mononuclear cells derived from peripheral blood were detected by real-time PCR, and the specific detection steps were AS follows:
1) peripheral blood mononuclear cell extraction
Adding 6mL of Ficoll-Paque PLUS into a 50mL centrifuge tube at room temperature; adding 4mL of fresh anticoagulated blood and PBS with the same amount into a 10mL centrifuge tube, uniformly mixing, carefully spreading the diluted blood sample on the Ficoll-Paque separating medium, then placing the centrifuge tube in a horizontal centrifuge, and centrifuging for 35min at the temperature of 19 ℃ and 400 g; after centrifugation, the material is divided into 4 layers which are sequentially from top to bottom: absorbing the plasma layer, the monocyte layer, the Ficoll-Paque PLUS and the erythrocyte layer, transferring the monocyte layer to another centrifuge tube, adding PBS with at least 3 times of volume, mixing uniformly, centrifuging at 19 ℃ and 400g for 15min, and discarding the supernatant; adding 6mL of PBS for resuspending the cells, centrifuging for 10min at the temperature of 19 ℃ by 100g, and removing the supernatant; then 1mL of PBS was added to resuspend the cells, and then the cells were transferred to a 1.5mL EP tube, centrifuged at 100g at 19 ℃ for 10min, and the supernatant was discarded and stored in a freezer at-80 ℃.
2) TRIzol method for extracting total RNA
Adding 1ml of TRIzol into the collected cell sediment at room temperature to crack the cell sediment until the liquid is clear and has no cell mass; adding 0.2mL of chloroform, violently shaking for 15 seconds, and standing for 5 minutes at room temperature; centrifugation was carried out at 12000rpm for 10 minutes at 4 ℃ and the supernatant (about 500ul) was taken and added to another EP tube; adding 0.5mL of precooled isopropanol, mixing the mixture gently and uniformly, and incubating the mixture for 30 minutes on ice; centrifuging at 12000rpm at 4 deg.C for 15min, and discarding the supernatant; 1mL of precooled 75% ethanol was added, centrifuged at 12000rpm at 4 ℃ for 5 minutes, and the supernatant was discarded; washing was repeated 2 times. The RNA precipitate was dried at room temperature, 20-50. mu.L of DEPC water was added, and the mixture was stored at-80 ℃ for further use.
3) Determination of RNA concentration and purity
mu.L of the RNA sample was pipetted into the buffer and the absorbance at 260nm and 280nm was determined. Based on the ratio of OD260/OD280, RNA quality was estimated. The ratio of OD260/OD280 is 1.8-2.0, and can meet the experimental requirements. When OD260/OD280 is less than 1.8, the pollution of protein in the solution is obvious; when OD260/OD280>2.2, it indicates that RNA has been degraded.
4) cDNA Synthesis
Reverse transcription Kit PrimeScriptRT reagent Kit (supplied by TaKaRa). The method comprises two steps, wherein the first step is to remove genome DNA, and the reaction system comprises the following steps: add total RNA (1. mu.g), 5 Xg DNA Eraser Buffer 2.0. mu.L, gDNA Eraser 1.0. mu.L, DEPC water make up to 10. mu.L, then PCR instrument 42 ℃ 2 min. Second step reverse transcription, reaction system: 10uL of the reaction solution from the first step, 1.0. mu.L of PrimeScript RT Enzyme Mix I, 1.0. mu.L of RT Primer Mix, RNase Free dH2O4.0. mu.L, PrimerScript Buffer 24.0. mu.L, 37 ℃, 15 min; taking out the reaction solution at 85 ℃ for 5s to obtain cDNA, and storing at-80 ℃ for later use.
5) PCR reaction
Taking out cDNA as a template for fluorescence quantification, wherein the reaction system comprises: 2 x SYBR Green mix 5uL, forward and reverse primers (10uM) each 1uL, template cDNA 1uL, RNase Free water 2uL, PCR amplification reaction is carried out on a fluorescence quantitative PCR instrument under the reaction condition of 95 ℃ for 1min, then 40 cycles are carried out at 95 ℃ for 20s and 60 ℃ for 1min to obtain the Ct value of each sample, beta-actin is used as an internal reference gene, and 2uL is adopted as the experimental result-△△CTThe method of (3) for analysis.
The results of the experiment are shown in fig. 1, and AS a result, mRNA expression of circRNA0003307 was found to be significantly up-regulated (P <0.001) in AS patients compared to healthy controls.
Pearson correlation analysis showed that the mRNA expression level of circRNA0003307 was positively correlated with the levels of ESR and CRP, which are disease activity indicators of AS patients, and the results are shown in FIG. 2.
Example 2circRNA0003307 interference sequence and uses thereof
This example designs and synthesizes a specific interference sequence si-circRNA0003307 (the nucleotide sequence is shown in SEQ ID No. 3) for the full-length sequence of circRNA0003307, infects synovial fibroblasts, makes the circRNA0003307 gene inhibit expression in cells, and further applies the interference gene vector to regulate the inflammatory response of synovial fibroblasts.
The specific cell infection method is as follows:
1. siRNA transfection procedure
1) The plate has a cell density of 50%.
2) The next day (after 24-36 hours) each well was transfected as follows:
a20 pmol siRNA was dissolved in 50ul Opti-mem serum free medium; b, dissolving 1ul lipo2000 in 50ul Opti-mem serum-free culture medium, uniformly mixing, and standing for 5min at room temperature; c, mixing two tubes of A B, and standing for 20 min.
3) During transfection, the 24-well plate medium was changed to serum-free medium at 400ul per well. And adding the C tube mix into the corresponding hole of the 24-hole plate, and replacing the hole with the serum culture medium for 4-6 hours.
4) Continuously culturing for 48h, collecting cells, and standing at-80 deg.C for use.
2. Plasmid transfection procedure
1) And (4) plating, and performing transfection properly when the cell density reaches more than 90% in the next day.
2) A0.8 ug DNA was dissolved in 50ul Opti-mem serum free medium; b, dissolving 2ul lipo2000 in 50ul Opti-mem serum-free culture medium, uniformly mixing, and standing for 5min at room temperature; c, mixing two tubes of A B, and standing for 20 min.
3) During transfection, the 24-well plate medium was changed to serum-free medium at 400ul per well. And adding the C tube mix into the corresponding hole of the 24-hole plate, and replacing the hole with the serum culture medium for 4-6 hours.
4) Continuously culturing for 48h, collecting cells, and standing at-80 deg.C for use.
As shown in FIG. 3, the si-circRNA0003307 group after the interference was able to reduce the mRNA and protein level expression of inflammatory cytokines TNF-. alpha.and TNFAIP2 in cells, compared to the circRNA0003307 control group.
After the interference with circRNA0003307, PI3K and AKT were significantly phosphorylated (fig. 4) and nuclear translocation (fig. 5) in synovial fibroblasts compared with the circRNA0003307 control group, but PI3K and AKT phosphorylation in synovial fibroblasts expressing circRNA0003307 in si-circRNA0003307 group were significantly inhibited compared with circRNA 0003307-control group, and the nuclear translocation effect of PI3K and AKT was also significantly inhibited in synovial fibroblasts, as shown in fig. 5.
Therefore, the inhibition effect of the interference circRNA0003307 on the inflammatory response of synovial fibroblasts in AS diseases is mainly realized through a PI3K/AKT signal pathway, and the interference circRNA0003307 can inhibit the activation of the synovial fibroblasts.
Sequence listing
<110> Anhui TCM university first subsidiary hospital (Anhui province TCM college)
Application and detection method of <120> circRNA0003307 gene
<160> 3
<170> SIPOSequenceListing 1.0
<210> 1
<211> 20
<212> DNA
<213> Artificial Sequence (Artificial Sequence)
<400> 1
ccctggagaa gagctacgag 20
<210> 2
<211> 20
<212> DNA
<213> Artificial Sequence (Artificial Sequence)
<400> 2
ggaaggaagg ctggaagagt 20
<210> 3
<211> 364
<212> DNA
<213> Artificial Sequence (Artificial Sequence)
<400> 3
ccatcgacga gtacaagccc caggatgcta ccaccaaccc gtccctgatc ctggccgcag 60
cacagatgcc cdcttaccag gagctggtgg aggaggcgat tgcctatggc cggaagctgg 120
gcgggtcaca agaggaccag attaaaaatg ctattgataa actttttgtg ttgtttggag 180
cagaaatact aaagaagatt ccgggccgag tatccacaga agtagacgca aggctctcct 240
ttgataaaga tgcgatggtg gccagagcca ggcggctcat cgagctctac aaggaagctg 300
ggatcagcaa ggaccgaatt cttataaagc tgtcatcaac ctgggaagga attcaggctg 360
gaaa 364
Claims (1)
1. An application of a preparation for detecting the expression quantity of circRNA0003307 gene in a peripheral blood mononuclear cell sample in preparing a ankylosing spondylitis detection preparation.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011274191.2A CN112210600B (en) | 2020-11-15 | 2020-11-15 | Application and detection method of circRNA0003307 gene |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011274191.2A CN112210600B (en) | 2020-11-15 | 2020-11-15 | Application and detection method of circRNA0003307 gene |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN112210600A CN112210600A (en) | 2021-01-12 |
| CN112210600B true CN112210600B (en) | 2022-02-08 |
Family
ID=74056881
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202011274191.2A Active CN112210600B (en) | 2020-11-15 | 2020-11-15 | Application and detection method of circRNA0003307 gene |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN112210600B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114350785B (en) * | 2022-01-05 | 2022-09-13 | 安徽中医药大学第一附属医院(安徽省中医院) | Application of circular RNA hsa _ circ _0000734 gene |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3054017A1 (en) * | 2015-02-03 | 2016-08-10 | Johann Wolfgang Goethe-Universität, Frankfurt am Main | Circular RNA for the diagnosis and treatment of cardiovascular diseases |
| DK3356556T3 (en) * | 2015-09-29 | 2020-03-02 | Max Delbrueck Centrum Fuer Molekulare Medizin Helmholtz Gemeinschaft | Method for diagnosing a disease by detecting circRNA in body fluids |
| GB201712184D0 (en) * | 2017-07-28 | 2017-09-13 | Owen Mumford Ltd | Medicament delivery device |
| CN110484613B (en) * | 2019-07-05 | 2022-11-22 | 新乡医学院第一附属医院 | Ankylosing spondylitis early diagnosis marker |
| CN111378740A (en) * | 2019-11-14 | 2020-07-07 | 中国人民解放军陆军军医大学第一附属医院 | Method for detecting immunological abnormality of circRNA in systemic lupus erythematosus lesion |
-
2020
- 2020-11-15 CN CN202011274191.2A patent/CN112210600B/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| CN112210600A (en) | 2021-01-12 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US8324183B2 (en) | Micro-RNA associated with rheumatoid arthritis | |
| EP2406402A2 (en) | Method to assess human allograft status from microrna expression levels | |
| EP3933050A1 (en) | Application of circular rna in preparing drug for treating systemic lupus erythematosus | |
| CN112210600B (en) | Application and detection method of circRNA0003307 gene | |
| CN111455059A (en) | Application of reagent for detecting and targeting biomarkers in oral squamous cell carcinoma | |
| Pattnaik et al. | Micro RNAs as potential biomarkers in tuberculosis: A systematic review | |
| CN112094913B (en) | Colorectal cancer biomarker and application thereof | |
| CN109402262B (en) | PCR detection kit for auxiliary diagnosis of neuroblastoma and method for detecting miR-199a-3p expression level | |
| CN101670117B (en) | Application of miR-146a in preparing medicine for curing gastricism | |
| CN113980968B (en) | Novel RA-marked long-chain non-coding RNA and application thereof | |
| CN111455061A (en) | Application of lncRNA biomarker in oral squamous cell carcinoma diagnosis and treatment | |
| CN111440874A (en) | Biomarker for diagnosing and treating oral squamous cell carcinoma | |
| CN111455060A (en) | Related biomarker for diagnosing and treating oral squamous cell carcinoma and application | |
| CN108410977B (en) | Ultra-early detection kit for serum miRNAs of alcoholic femoral head necrosis patient | |
| CN114350785B (en) | Application of circular RNA hsa _ circ _0000734 gene | |
| CN112410439B (en) | Application of chi-miR-128-3p as goat follicle maturation miRNA marker | |
| CN111826433B (en) | Application of LncRNA in prognosis evaluation of diabetes and early warning of recurrent abortion | |
| CN109172593B (en) | Application of miR-516a as target for treating bladder cancer | |
| CN111440875A (en) | Biomarker-based diagnosis and use for treating cancer | |
| CN107523641B (en) | Serum miRNAs biomarkers and application thereof | |
| CN114277126B (en) | Application of hsa _ miR-486-5p and ETS-1 gene in rheumatoid arthritis diagnosis and treatment reagent | |
| CN111575381A (en) | Novel use of biomarkers | |
| CN111560437A (en) | Biomarkers for predicting oral squamous carcinoma and their use in therapy | |
| Lyu et al. | CRISPR/Cas9-based knockout of miR-487b-3p accelerates the cell proliferation of primary goat myoblast by relieving its inhibition of IRS1 | |
| CN115261482B (en) | Application of miR-4256 in treatment, diagnosis and prognosis evaluation of gastric cancer |
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 |