CN114848666A - Application of miRNA-203a-3p mimic in preparation of medicine for treating idiopathic pulmonary fibrosis - Google Patents

Application of miRNA-203a-3p mimic in preparation of medicine for treating idiopathic pulmonary fibrosis Download PDF

Info

Publication number
CN114848666A
CN114848666A CN202210475510.9A CN202210475510A CN114848666A CN 114848666 A CN114848666 A CN 114848666A CN 202210475510 A CN202210475510 A CN 202210475510A CN 114848666 A CN114848666 A CN 114848666A
Authority
CN
China
Prior art keywords
mirna
mimic
pulmonary fibrosis
preparation
idiopathic pulmonary
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.)
Pending
Application number
CN202210475510.9A
Other languages
Chinese (zh)
Inventor
龚琳婧
王新元
姜法明
赵悦安
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
West China Hospital of Sichuan University
Original Assignee
West China Hospital of Sichuan University
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by West China Hospital of Sichuan University filed Critical West China Hospital of Sichuan University
Priority to CN202210475510.9A priority Critical patent/CN114848666A/en
Publication of CN114848666A publication Critical patent/CN114848666A/en
Pending legal-status Critical Current

Links

Images

Classifications

    • 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
    • A61K31/713—Double-stranded nucleic acids or oligonucleotides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • 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
    • C12Q2600/118—Prognosis of disease development
    • 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

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biochemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Analytical Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Wood Science & Technology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Zoology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Physics & Mathematics (AREA)
  • Biophysics (AREA)
  • Biotechnology (AREA)
  • Immunology (AREA)
  • Microbiology (AREA)
  • Pathology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pulmonology (AREA)
  • General Engineering & Computer Science (AREA)
  • Epidemiology (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)

Abstract

The invention discloses an application of miRNA-203a-3p mimics in preparation of a medicament for treating idiopathic pulmonary fibrosis. The nucleotide sequence of the miRNA-203a-3p mimic is shown in SEQ ID NO. 1. The miRNA-203a-3p mimic designed by the invention can relieve collagen deposition of lung tissues and structural disorder of the lung tissues by inhibiting EMT process of alveolar epithelial cells and fibroblast activation, and shows that the miRNA-203a-3p mimic can be applied to preparation of medicaments for treating idiopathic pulmonary fibrosis.

Description

Application of miRNA-203a-3p mimic in preparation of medicine for treating idiopathic pulmonary fibrosis
Technical Field
The invention belongs to the technical field of genetic engineering, and particularly relates to an application of a miRNA-203a-3p mimic in preparation of a medicament for treating idiopathic pulmonary fibrosis.
Background
Idiopathic Pulmonary Fibrosis (IPF) is the most common form of idiopathic interstitial pneumonia, a chronic, progressive, fibrotic, interstitial disease of the lung. The disease causes are unknown, most of the disease causes are in the middle-aged and the elderly (about 55-75 years old in diagnosis), and the median survival time after diagnosis is about 3 years. The incidence of IPF is increasing year by year, and mortality rates are high due to frequent misdiagnosis and inappropriate immunosuppressive therapy. Currently, treatment regimens for IPF patients are limited to two FDA-approved clinical drugs, pirfenidone and nintedanib. Both of these drugs, while proven to slow disease progression, do not prevent or reverse fibrosis. Eventually, the vast majority of IPF patients die from respiratory failure. Therefore, a need to explore the key molecular mechanism of IPF generation and development and to provide a theoretical basis for personalized diagnosis and development of targeted drugs by using advanced genomic technology and system biological methods is urgently needed.
Abnormal repair of alveolar epithelial cells and sustained activation of myofibroblast phenotype (epithelial and fibroblasts) are the main features of pulmonary fibrosis. Micro RNA (microRNA, miRNA) is a kind of endogenous multifunctional non-coding RNA consisting of 22-25 nucleotides, and acts on a 3 '-non-coding region (3' -UTR) of target mRNA to regulate gene expression horizontally after transcription. At present, little is known about the role of miRNAs in the pathogenesis of IPF.
Disclosure of Invention
Aiming at the defects in the prior art, the invention provides the application of the miRNA-203a-3p mimic in preparing the medicine for treating idiopathic pulmonary fibrosis, and solves the problems of lack of effective treatment means, poor treatment effect and the like of the existing idiopathic pulmonary fibrosis.
In order to achieve the purpose, the technical scheme adopted by the invention for solving the technical problems is as follows:
application of miRNA-203a-3p mimics in preparation of medicines for treating idiopathic pulmonary fibrosis.
Further, the nucleotide sequence of the miRNA-203a-3p mimic is shown in SEQ ID NO. 1. The specific sequence is as follows:
5’-GUGAAAUGUUUAGGACCACUAG-3’(SEQ ID NO.1)
furthermore, the miRNA-203a-3p mimic is a gene which has more than 80% of homology with the nucleotide sequence shown as SEQ ID NO.1 and expresses the same functional protein.
Further, the miRNA-203a-3p mimics can simultaneously regulate alveolar epithelial cell function and fibroblast function.
The miRNA-203a-3p mimic is applied to the preparation of a pharmaceutical composition for treating idiopathic pulmonary fibrosis, and the pharmaceutical composition comprises the miRNA-203a-3p mimic and/or an active ingredient for promoting the overexpression of the miRNA-203a-3p mimic, and an adjuvant.
The miRNA-203a-3p mimic is applied to preparation of reagents for detecting idiopathic pulmonary fibrosis diseases and/or prognosis judgment.
The invention has the beneficial effects that:
the invention discloses a miRNA-203a-3p mimic for treating idiopathic pulmonary fibrosis and application thereof in preparation of related therapeutic drugs, wherein a nucleotide sequence of the miRNA-203a-3p mimic is shown in SEQ ID No.1, and the miRNA-203a-3p mimic can relieve collagen deposition of lung tissues and structural disorder of the lung alveoli tissues by inhibiting EMT process of alveolar epithelial cells and activation of fibroblasts, so that the miRNA-203a-3p mimic can be applied to preparation of drugs for treating idiopathic pulmonary fibrosis.
Drawings
FIG. 1 is a diagram illustrating the detection of the expression level of miRNA-203a-3p in lung tissue of a patient with IPF;
FIG. 2 shows the result of Transwell assay of A549 cells over-expressed by miRNA-203a-3p mimetics;
FIG. 3 shows the detection results of A549 cell scratch test of miRNA-203a-3p mimic overexpression;
FIG. 4 is a graph showing the effect of miRNA-203a-3p mimetic overexpression on the amount of ZO-1 and Vimentin protein expression in cells;
FIG. 5 is a graph showing the effect of miRNA-203a-3p mimetic overexpression on the amount of fibrinectin and alpha-SMA protein expressed in a cell;
FIG. 6 is a H & E staining assay of cells after overexpression of miRNA-203a-3p mimetics.
Detailed Description
The following description of the embodiments of the present invention is provided to facilitate the understanding of the present invention by those skilled in the art, but it should be understood that the present invention is not limited to the scope of the embodiments, and it will be apparent to those skilled in the art that various changes may be made without departing from the spirit and scope of the invention as defined and defined in the appended claims, and all matters produced by the invention using the inventive concept are protected.
Example 1 expression of miRNA-203a-3p in IPF patients
Lung tissue samples obtained from GSE27430 dataset, 13 samples from the remnant of surgical biopsy, or lung tissue from IPF patient receiving lung transplant; 12 samples were from disease-free margin normal lung tissue from excised specimens. Pathological diagnosis of IPF is based on typical microscopic findings consistent with common interstitial pneumonia. The data set expression matrix is based on the analysis of the Limma package in the R language, the screening conditions of the differential miRNAs are adj.P.Val <0.05 and | logFC | > or more than 1, and the miRNA-203a-3p is found to be obviously low expressed in the lung tissue of the IPF patient (figure 1). It is suggested that the over-expression of miRNA-203a-3p and the mimics thereof in lung tissues has potential effects of treating IPF.
Example 2 Synthesis of miRNA-203a-3p mimetics
1. Extraction of small RNA
(1) The six-well plate was removed, the medium was discarded, and washed once with pre-cooled PBS.
(2) 1mL of RNAioso for small RNA was added to each well and allowed to stand on ice for 10 min.
(3) The lysate was transferred to a 1.5mL centrifuge tube, 200. mu.L chloroform was added, the centrifuge tube cap was closed, the mixture was mixed until the solution was emulsified milky white, and the mixture was allowed to stand on ice for 10 min.
(4) Centrifuge at 4 ℃ at 12000g for 15 min. After centrifugation, the lysate is divided into three layers from bottom to top: the lower layer is red and is an organic phase; the middle layer is white and is a protein layer; the upper layer is a colorless supernatant layer. The colorless supernatant is required for extracting RNA.
(5) Transferring the supernatant to a newly taken centrifugal tube by using a pipette gun, adding isopropanol with the same volume, turning the centrifugal tube upside down, fully mixing the mixture, and standing the mixture on ice for 10 min.
(6) Centrifugation is carried out at 4 ℃ for 12000g for 10 min. After centrifugation, a white RNA precipitate was visible at the bottom of the tube, the supernatant was carefully discarded, 1mL of 75% ethanol (prepared with absolute ethanol and DEPC water) was added, and the tube walls were washed by gentle inversion. Centrifuging at 4 deg.C, 7500g for 5min, and discarding supernatant.
(7) Opening the centrifugal tube cover, drying at room temperature for 3min, and adding a proper amount of RNase-free water to dissolve the precipitate.
2. Synthesis of cDNA
Reverse transcription reaction is carried out by using a primer sequence shown in SEQ ID NO. 2. The reaction mixture was prepared as shown in Table 1 by working on ice.
TABLE 1 miRNA cDNA reaction System
Figure BDA0003625299340000041
After mixing well, reverse transcription reaction was performed with U6 as an internal reference, and the reaction procedure was as follows: 30min at 16 ℃; 30min at 37 ℃; 5min at 85 ℃; storing at 4 ℃.
Reverse transcription primer: 5'-GTCGTATCCAGTGCAGGGTCCGAGGTATTCGCACTGGATACGACACTTTA-3' (SEQ ID NO.2)
3.qRT-PCR
Primer sequences shown in SEQ ID NO.3 and SEQ ID NO. 4 are used for carrying out real-time fluorescence quantitative PCR reaction, 3 multiple holes are set, and the whole process of loading should be protected from light. The reaction system is as follows:
TABLE 2 miRNA cDNA reaction System
Figure BDA0003625299340000051
Uniformly mixing, loading on a machine, and setting reaction conditions as follows: step 1: 30s at 95 ℃; step 2: 5s at 95 ℃; 60 ℃ 30s (40 cycles); step 3: melt Curve.
And finally, calculating and analyzing the results of the three independent experiments by adopting a 2-delta Ct method.
Example 3 miRNA-203a-3p mimetics in vitro cell assay
1. Transwell experiment
(1) 1 × 10 transfected with miR-mici or miR-NC 4 A549 cells are inoculated in an upper chamber (24-well plate, aperture is 8um) of a Transwell chamber, 500-600 mu L of PBS and TGF-beta 1(10ng/mL) are respectively added in a lower chamber to induce migration of the A549 cells for 12h, and a PBS group and a TGF-beta 1 experimental group are formed.
(2) Carefully taking out the upper chamber of the small chamber by using a pair of tweezers, sucking the liquid, transferring the liquid into a small hole of a 24-hole plate containing 1mL of 4% paraformaldehyde, and fixing the liquid at room temperature for 15-30 min;
(3) staining cells with 0.2% crystal violet solution for 20min, soaking in PBS for several times to remove excessive crystal violet, and slightly wiping off cells on PET membrane without membrane migration with cotton swab
(4) The amount of migrated cells in each group was estimated after photographing under an inverted microscope.
As shown in figure 2, a Transwell experiment carried out on A549 cells shows that the migration function of the A549 cells can be obviously promoted by stimulating the A549 cells for 24h by 10ng/mL of TGF-beta 1, and the function is obviously inhibited after the miRNA-203a-3p mimics are transfected.
2. Scratch test
(1) A549 cells are inoculated in a 6-well plate, and miR-mimic or miR-NC is transfected when the cells are fused to 70-80%.
(2) 1.5mL of EP tube, 5. mu.L Lipofectamine2000 liposome reagent was added to 100. mu.L of opti-DMEM medium (tube A); in addition, 2 mu g of miR-mici or miR-NC is added into 100 mu L of opti-DMEM medium in 1.5mL of EP tube, and placed for 30min at room temperature (tube B).
(3) Mix the tube A and tube B solutions (final volume 200. mu.L) and let stand at room temperature for 5-10 min.
(4) Discarding the culture medium in the 6-well plate, adding 1.8mL of fresh 1640 serum-free culture medium, adding a 200 mu L A tube + B tube mixed solution, transfecting for 8h, observing the cell state, and continuously culturing for 24h without replacing the culture medium if the state is good; if the state is not good, replacing the fresh culture medium to continue culturing for 24h
(5) A monolayer of A549 cells were scratched with a 200. mu.L tip of a sterile pipette tip, the transfected A549 cells were treated with 10ng/mL TGF-. beta.1 for 48h, and the cell migration (degree of fusion of cells on both sides of scratch) was observed under an inverted microscope.
As shown in figure 3, scratch experiments on A549 cells show that the function of stimulating A549 cells by 10ng/mL TGF-beta 1 for 24h can obviously promote the migration function of the cells, and the function of the cells is obviously inhibited after the miRNA-203a-3p mimics are transfected.
3. Western blot experiment
(1) A549 cells are stimulated for 24 hours by adopting 10ng/mL TGF-beta 1, then miRNA-203a-3p mimics are transfected, and the change of ZO-1 and Vimentin protein expression quantity of the A549 cells is detected by a Western blot experiment.
As shown in FIG. 4, before the miRNA-203a-3p mimics are transfected, the expression level of both ZO-1 and Vimentin proteins is obviously increased; after the miRNA-203a-3p mimics are transfected, the ZO-1 and Vimentin protein surface levels of the TGF-beta 1 stimulated A549 cells are not obviously changed compared with those of a control group, and are obviously reduced compared with a single TGF-beta 1 stimulated group.
(2) The method comprises the steps of stimulating HFL1 cells for 24 hours by adopting 10ng/mL TGF-beta 1, then transfecting miRNA-203a-3p mimics, and detecting the change of the expression quantity of fibrinectin and alpha-SMA protein of HFL1 cells by Western blot experiment.
As shown in FIG. 5, the expression level of both Fibronectin and alpha-SMA protein is obviously increased before the miRNA-203a-3p mimics are transfected; after the miRNA-203a-3p mimics are transfected, the Fibronectin and alpha-SMA protein surface levels of HFL1 cells stimulated by TGF-beta 1 are not changed remarkably compared with a control group, and are reduced remarkably compared with a single TGF-beta 1 stimulation group.
Example 4 in vivo animal experiments
Male C57BL/6J mice (6-8 weeks old) were housed in a specific pathogen free environment (SPF) and were allowed free access to water. Mice were intratracheally injected with bleomycin (50 mg/kg concentration in 50 μ L saline) or an equal volume of saline to form BLM group (bleomycin group) and CON group (control group), respectively. To specifically over-express miRNA-203a-3p in mouse lung fibroblasts, the experimental group of BLM + miRNA was formed by nasally administering miRNA-203a-3p agomir (15nmol in 30 μ L PBS) to the BLM group on day 5 and every 4 days thereafter. Then 3 groups of mice were sacrificed on day 21 (n ═ 6). Lungs were taken, fixed in 4% paraformaldehyde for 2 days, paraffin embedded, sectioned at 4 μm thickness, and stained with H & E and MASSON.
(see FIG. 6)
As shown in fig. 6, H & E staining showed alveolar inflammatory cell infiltration, fibrinolysis, and thickening of the spaces observed in lung tissue sections after 21 weeks of BLM exposure; and after the artificially synthesized miRNA-203a-3p mimics are over-expressed, the pulmonary fibrosis change of the mice is remarkably inhibited. Using Masson trichrome staining, we found that BLM mice induced severe collagen deposition in lung tissue 21 days after tracheal instillation compared to control mice. Overexpression of the synthetic miRNA-203a-3p mimic reduced BLM-induced collagen deposition in lung tissue compared to the BLM group (fig. 6).
Therefore, according to the detection results, the miRNA-203a-3p mimics have a potential effect of treating IPF.
Sequence listing
<110> Sichuan university Hospital in western China
Application of <120> miRNA-203a-3p mimic in preparation of medicine for treating idiopathic pulmonary fibrosis
<160> 4
<170> SIPOSequenceListing 1.0
<210> 1
<211> 22
<212> RNA
<213> Artificial Sequence (Artificial Sequence)
<400> 1
gugaaauguu uaggaccacu ag 22
<210> 2
<211> 50
<212> DNA
<213> Artificial Sequence (Artificial Sequence)
<400> 2
gtcgtatcca gtgcagggtc cgaggtattc gcactggata cgacacttta 50
<210> 3
<211> 21
<212> DNA
<213> Artificial Sequence (Artificial Sequence)
<400> 3
acgtatgcga tcaccaggat t 21
<210> 4
<211> 18
<212> DNA
<213> Artificial Sequence (Artificial Sequence)
<400> 4
cagtgcaggg tccgaggt 18

Claims (6)

  1. Application of miRNA-203a-3p mimics in preparation of medicines for treating idiopathic pulmonary fibrosis.
  2. 2. The use of claim 1, wherein the nucleotide sequence of the miRNA-203a-3p mimetic is set forth in SEQ ID No. 1.
  3. 3. The use of claim 1, wherein the miRNA-203a-3p mimetic is a gene that has more than 80% homology with the nucleotide sequence set forth in SEQ ID No.1 and expresses the same functional protein.
  4. 4. The use of claim 1, wherein the miRNA-203a-3p mimetic modulates both alveolar epithelial cell function and fibroblast function.
  5. 5. Use of a miRNA-203a-3p mimetic according to claim 1 for the preparation of a pharmaceutical composition for the treatment of idiopathic pulmonary fibrosis, said pharmaceutical composition comprising a miRNA-203a-3p mimetic and/or an active ingredient which promotes overexpression of a miRNA-203a-3p mimetic, and an adjuvant.
  6. 6. Use of the miRNA-203a-3p mimetic of claim 1 for the preparation of a reagent for detecting idiopathic pulmonary fibrosis and/or prognosis.
CN202210475510.9A 2022-04-29 2022-04-29 Application of miRNA-203a-3p mimic in preparation of medicine for treating idiopathic pulmonary fibrosis Pending CN114848666A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202210475510.9A CN114848666A (en) 2022-04-29 2022-04-29 Application of miRNA-203a-3p mimic in preparation of medicine for treating idiopathic pulmonary fibrosis

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202210475510.9A CN114848666A (en) 2022-04-29 2022-04-29 Application of miRNA-203a-3p mimic in preparation of medicine for treating idiopathic pulmonary fibrosis

Publications (1)

Publication Number Publication Date
CN114848666A true CN114848666A (en) 2022-08-05

Family

ID=82635277

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202210475510.9A Pending CN114848666A (en) 2022-04-29 2022-04-29 Application of miRNA-203a-3p mimic in preparation of medicine for treating idiopathic pulmonary fibrosis

Country Status (1)

Country Link
CN (1) CN114848666A (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN116004628A (en) * 2023-01-03 2023-04-25 苏州大学 miRNA target spot for preventing or treating chronic pain and application thereof

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
JAMES N. TSOPORIS等: "A longitudinal study of alterations of circulating DJ-1 and miR203a-3p in association to olanzapine medication in a sample of first episode patients with schizophrenia", 《JOURNAL OF PSYCHIATRIC RESEARCH》 *
JUAN LI等: "CircRNA TADA2A relieves idiopathic pulmonary fibrosis by inhibiting proliferation and activation of fibroblasts", 《CELL DEATH AND DISEASE》 *
QI FAN等: "MiR-203a-3p regulates TGF-β1-induced epithelial–mesenchymal transition (EMT) in asthma by regulating Smad3 pathway through SIX1", 《BIOSCIENCE REPORTS》 *
任亦频等: "过表达miR-203a-3p对脂多糖致大鼠急性肺损伤后肺纤维化的影响及其机制", 《安徽医科大学学报》 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN116004628A (en) * 2023-01-03 2023-04-25 苏州大学 miRNA target spot for preventing or treating chronic pain and application thereof

Similar Documents

Publication Publication Date Title
CN110592216B (en) Application of LRSAM1 as hepatocellular carcinoma molecular marker
CN111304324B (en) Application of ALPL gene as diagnosis and treatment target of lung adenocarcinoma and lung adenocarcinoma metastasis
CN114848666A (en) Application of miRNA-203a-3p mimic in preparation of medicine for treating idiopathic pulmonary fibrosis
CN111617249A (en) Application of hsa _ circ _0007444 in preparation of medicine for treating ovarian cancer
CN114191540A (en) Application of CTRP13 in preparing medicine for preventing and treating vascular and tumor diseases
CN107893115B (en) ALKBH1 gene and application of expression product thereof in preparation of kit for diagnosing tumors and drugs for treating tumors
CN109939222B (en) Medical application of CREG protein for promoting skeletal muscle regeneration
CN114457158B (en) Application of Hsa_circ_0006867 serving as esophageal cancer molecular target in preparation of medicines and kits
CN113171459A (en) Application of FUNDC1 in preparing medicine for preventing and treating vascular and tumor diseases
CN116509887B (en) Application of gentianella acuta-derived Gen-miR-5 in preparation of medicament for preventing and treating myocardial hypertrophy
CN107988223B (en) SaRNA for activating PTPRO gene expression and application thereof in tumor stem cell treatment
CN111926015A (en) Oligonucleotide, viral vector and application thereof and RNAi pharmaceutical preparation
CN112063710A (en) Diagnostic and therapeutic uses of long non-coding RNAs
CN111110693B (en) Application of agent for down-regulating expression of circular gene in preparation of medicine for preventing and/or treating pulmonary fibrosis and medicine
Luo et al. MALAT1 mediates miR-206/CDC42/PAK1/Paxillin signaling axis to alleviate erectile dysfunction in rats
CN110951880B (en) Application of reagent for detecting lncRNA marker of hypopharynx cancer in preparation of product for diagnosing hypopharynx cancer
CN117159581B (en) Application of piRNA antisense nucleotide pharmaceutical composition as aortic valve calcification prevention and treatment drug
CN113368242B (en) Application of non-small cell lung cancer inhibition target
CN110257377B (en) Target linc00998 gene inhibitor for inhibiting human malignant brain glioma and application thereof
CN113122638B (en) Application of hsa-novel_circ_0006787 molecule in liver cancer treatment
CN108410986B (en) CDH6 promotes osteosarcoma growth and metastasis
CN114432334B (en) Application of lnc-BIHAA1 in preparation of medicines for preventing and/or treating hepatic fibrosis
CN111235262B (en) Diagnostic product and therapeutic drug thereof and application of diagnostic product and therapeutic drug in osteoarthritis
CN115887570B (en) Application of longhairy antenoron herb extract in preparation of products for regeneration and repair after intestinal mucosa injury
CN114149499B (en) Monoclonal antibodies against human EMC10 and their use in the treatment and/or prevention of obesity

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
RJ01 Rejection of invention patent application after publication

Application publication date: 20220805

RJ01 Rejection of invention patent application after publication