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WO2024128688A1 - Nouveaux biomarqueurs pour le diagnostic ou le pronostic de la cystite interstitielle et leur utilisation - Google Patents

Nouveaux biomarqueurs pour le diagnostic ou le pronostic de la cystite interstitielle et leur utilisation Download PDF

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Publication number
WO2024128688A1
WO2024128688A1 PCT/KR2023/020158 KR2023020158W WO2024128688A1 WO 2024128688 A1 WO2024128688 A1 WO 2024128688A1 KR 2023020158 W KR2023020158 W KR 2023020158W WO 2024128688 A1 WO2024128688 A1 WO 2024128688A1
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hsa
mir
interstitial cystitis
expression level
group
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PCT/KR2023/020158
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English (en)
Korean (ko)
Inventor
고광진
이규성
김홍숙
김종수
이정희
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Sungkyunkwan University
Samsung Life Public Welfare Foundation
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Sungkyunkwan University
Samsung Life Public Welfare Foundation
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Priority claimed from KR1020230169219A external-priority patent/KR20240097996A/ko
Application filed by Sungkyunkwan University, Samsung Life Public Welfare Foundation filed Critical Sungkyunkwan University
Publication of WO2024128688A1 publication Critical patent/WO2024128688A1/fr
Anticipated expiration legal-status Critical
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    • 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

Definitions

  • the present invention relates to a new biomarker for diagnosing or predicting prognosis of interstitial cystitis and its use.
  • Interstitial cystitis is a chronic bladder inflammation that can be caused by a variety of causes, such as bacterial or viral infection, changes in bladder epithelial cell permeability, immune cell infiltration, autoimmune disease, stress, and hormonal abnormalities, without a clear cause. It is a disease. It mainly causes recurrent pelvic pain and pressure in the bladder area, and is accompanied by one or more irritating urinary symptoms such as urgency and frequent urination, which reduces the patient's quality of life.
  • interstitial cystitis There is still no accurate and specific diagnostic method for interstitial cystitis. Diagnosis is possible when characteristic Hurner lesions are observed on cystoscopic examination, but these lesions are not observed in all patients. Currently, interstitial cystitis is diagnosed by excluding other possible diseases, so it takes a lot of time and test costs to diagnose, and there is a risk of missing the appropriate treatment time.
  • One aspect of the present invention aims to provide a composition and kit for diagnosing or predicting prognosis of interstitial cystitis.
  • the purpose of the present invention is to provide a method of providing information for diagnosing or predicting prognosis of interstitial cystitis.
  • One aspect of the present invention is hsa-miR-1273c, hsa-miR-142-3p, hsa-miR-142-5p, hsa-miR-144-3p, hsa-miR-150-5p, hsa-miR-16- 5p, hsa-miR-185-5p, hsa-miR-31-5p, hsa-miR-3934-5p, hsa-miR-6126, hsa-miR-8485, hsa-miR-941, hsa-let-7a- 5p, hsa-let-7d-3p, hsa-let-7e-5p, hsa-let-7f-5p, hsa-miR-10a-3p, hsa-miR-10b-5p, hsa-miR-1260b, hsa- miR-200b-5p,
  • Interstitial cystitis used in the present invention is a chronic bladder inflammatory disease of unknown cause accompanied by symptoms such as urinary pain, pelvic pain, and pain in the bladder area, as well as urinary symptoms such as frequent urination and urgency.
  • There is still no single accurate diagnostic method for interstitial cystitis and there is no interstitial cystitis biomarker with excellent specificity and sensitivity that can be used to predict diagnosis or treatment prognosis.
  • diagnosis means confirming the presence or characteristics of a pathological condition in an individual who has not yet been diagnosed or has been diagnosed. Diagnosis in the present invention may be to confirm whether or not there is a possibility of progression to interstitial cystitis using a biomarker.
  • prognosis refers to determining whether a diagnosed individual has recurrence, metastasis, drug responsiveness, resistance, etc. before/after treatment.
  • a biomarker may be used to predict drug responsiveness and recurrence after treatment of a patient with interstitial cystitis.
  • biomarkers are generally detectable substances in biological samples and include all organic biomolecules such as polypeptides, proteins, nucleic acids, genes, lipids, glycolipids, glycoproteins, sugars, etc. that can detect biological changes.
  • miRNA used in the present invention is also called micro RNA, and is a 21 to 23 non-coding RNA that regulates gene expression post-transcriptionally by promoting the degradation of target RNA or suppressing their translation. It means RNA.
  • miRNA is transcribed into a precursor about 70-80 nt (nucleotide) long with a hairpin structure called pre-miRNA, and then cleaved by Dicer, an RNAse III enzyme, to produce a mature form. More than 30% of human miRNAs exist in clusters, and are transcribed as a single precursor and then undergo a cleavage process to form the final mature miRNA.
  • miRNAs consist of specific miRNAs that show specific expression level changes in interstitial cystitis patients identified through next-generation sequencing (NGS), and are presented as biomarkers for diagnosing or predicting prognosis of interstitial cystitis. It can be.
  • NGS next-generation sequencing
  • the NGS has the multiplexing ability to perform hundreds of thousands of reactions simultaneously, and sequencing is possible even with a small amount of sample.
  • NGS has somewhat different specific application techniques depending on the commercialized technology, but generally uses clonal amplification, massively parallel sequencing, and a new sequencing method that has a different mechanism of action from the Sanger method.
  • Commercialized technologies include the 454 GS improved FLX model sequencer released by Roche in 2007, Genome Analyzer HiSeq released by Illumina in 2006, and SOLiD released by Applied Biosystems in 2007. These three platforms have in common the adoption of clone amplification technology, abandoning complex library construction and cloning processes, massively parallel sequencing technology that can process large quantities at once, and cyclic sequencing. By determining the base sequence through sequencing by synthesis, a complicated electrophoresis process was eliminated. In addition, short reads read using the shotgun method are arranged by a computer, and an algorithm is used to find duplicate parts and complete the whole.
  • the miRNA may be separated from exosomes.
  • exosome is a type of EVs (extracellular vesicles), small vesicles composed of a lipid bilayer that cells release to the outside. They are secreted from various cells and are known to have a diameter of approximately 30 to 200 nm. there is. These exosomes contain proteins, lipids, and nucleic acids (e.g., DNA, mRNA, and miRNA) similar to those inside the parent cell, and are applied in various fields such as disease diagnosis, bioinformatics, and drug delivery systems.
  • EVs extracellular vesicles
  • small vesicles composed of a lipid bilayer that cells release to the outside. They are secreted from various cells and are known to have a diameter of approximately 30 to 200 nm. there is.
  • These exosomes contain proteins, lipids, and nucleic acids (e.g., DNA, mRNA, and miRNA) similar to those inside the parent cell, and are applied in various fields such as disease diagnosis, bioinformatics
  • the exosomes can be obtained from samples such as whole blood, plasma, serum, lymph, saliva, urine, and tissue, and can be isolated by applying or modifying conventional exosome isolation methods without limitation depending on the type of sample.
  • exosome-derived miRNAs can be used alone or in combination of two or more as biomarkers for diagnosing or predicting prognosis of interstitial cystitis.
  • the miRNAs are hsa-miR-1273c, hsa-miR-142-3p, hsa-miR-142-5p, hsa-miR-144-3p, hsa-miR-150-5p, hsa-miR-16 -5p, hsa-miR-185-5p, hsa-miR-31-5p, hsa-miR-3934-5p, hsa-miR-6126, hsa-miR-8485, hsa-miR-941, hsa-let-7a -5p, hsa-let-7d-3p, hsa-let-7e-5p, hsa-let-7f-5p, hsa-miR-10a-3p, hsa-miR-10b-5p, hsa-miR-1260b, hsa -miR-200b-5p
  • the miRNAs are hsa-miR-1273c, hsa-miR-142-3p, hsa-miR-142-5p, hsa-miR-144-3p, hsa-miR-150-5p, hsa-miR-16-5p , hsa-miR-185-5p, hsa-miR-31-5p, hsa-miR-3934-5p, hsa-miR-6126, hsa-miR-8485, hsa-miR-941, hsa-let-7a-5p , hsa-let-7d-3p, hsa-let-7e-5p, hsa-let-7f-5p, hsa-miR-10a-3p, hsa-miR-10b-5p, hsa-miR-1260b, hsa-miR -200b-5p
  • the miRNA is hsa-miR-1273c, hsa-miR-142-3p, hsa-miR-142-5p, hsa-miR-144-3p, hsa-miR-150-5p, hsa-miR-185 -5p, hsa-miR-3934-5p, hsa-miR-6126, hsa-miR-8485, hsa-let-7d-3p, hsa-miR-10a-3p, hsa-miR-30d-5p, hsa-miR It may be one or more selected from the group consisting of -374b-5p, hsa-miR-423-3p, hsa-miR-532-3p, and hsa-miR-874-3p.
  • the agent may be selected from primers, probes, and antisense nucleotides that bind complementary or specifically to miRNA.
  • binding means binding according to the base of the polynucleotide constituting the target sequence, where adenine hydrogen bonds with thymine and guanine hydrogen bonds with cytosine, respectively.
  • specifically binding means that the binding ability to the target substance is superior to that of other substances to the extent that the presence or absence of the target substance can be detected by binding.
  • a “primer” is a nucleic acid sequence with a short free 3-terminal hydroxyl group, a single-stranded oligomer that can base pair with a complementary template and serves as a starting point for copying the template strand. It means nucleotide (single strand oligonucleotide).
  • the primers can initiate DNA synthesis in the presence of four different nucleoside triphosphates and a reagent for polymerization (i.e., DNA polymerase or reverse transcriptase) in an appropriate buffer solution and temperature.
  • the primer consists of a primer pair of sense and antisense nucleic acids with a sequence of 7 to 50 nucleotides, and is 15 at a level that does not change the basic properties of the primer that serves as the starting point of DNA synthesis. It can have a sequence of ⁇ 30 nucleotides.
  • probe refers to a linear oligomer of natural or modified monomers or linkages, including deoxyribonucleotides and ribonucleotides, and specifically hybridizing to the target nucleotide sequence. It can exist naturally or be artificially synthesized.
  • primers and probes may, if desired, contain labels detectable directly or indirectly by spectroscopic, photochemical, biochemical, immunochemical or chemical means.
  • the detectable label is a label material capable of generating a detectable signal, and may include a fluorescent substance such as Cy3, Cy5, etc.
  • the detectable label can confirm the hybridization results of nucleic acids.
  • Such a composition for diagnosing or predicting prognosis of interstitial cystitis can effectively determine whether there is interstitial cystitis or the treatment prognosis of interstitial cystitis by measuring the expression level of the biomarker, that is, miRNA.
  • the composition includes hsa-miR-1273c, hsa-miR-142-3p, hsa-miR-142-5p, hsa-miR-144-3p, hsa-miR-150-5p, hsa-miR-185-5p, hsa-miR-3934-5p, hsa-miR-6126, hsa-miR-8485, hsa-let-7d-3p, hsa-miR-10a-3p, hsa-miR-30d- Containing an agent for measuring the expression level of one or more miRNAs selected from the group consisting of 5p, hsa-miR-374b-5p, hsa-miR-423-3p, hsa-miR-532-3p and hsa-miR-874-3p It may be.
  • one aspect of the present invention provides a kit for diagnosing or predicting prognosis of interstitial cystitis, including the composition.
  • the "kit for diagnosing or predicting prognosis of interstitial cystitis" used in the present invention is a test subject, more specifically, a kit that can diagnose or predict prognosis through biological samples collected from individuals who have not been diagnosed with interstitial cystitis or patients with interstitial cystitis. It refers to a substance, through which the test subject's interstitial cystitis or treatment prognosis can be quickly, accurately, and easily diagnosed.
  • hsa-miR-1273c hsa-miR-142-3p, hsa-miR-142-5p, hsa-miR-144-3p, hsa-miR-150-5p, hsa-miR-16-5p, hsa -miR-185-5p, hsa-miR-31-5p, hsa-miR-3934-5p, hsa-miR-6126, hsa-miR-8485, hsa-miR-941, hsa-let-7a-5p, hsa -let-7d-3p, hsa-let-7e-5p, hsa-let-7f-5p, hsa-miR-10a-3p, hsa-miR-10b-5p, hsa-miR-1260b, hsa-miR-200b -5p, hsa-mi
  • the kit may include, without limitation, a diagnostic kit based on conventional RNA expression analysis.
  • the kit may be one or more selected from the group consisting of a polymerase chain reaction (PCR) kit, a reverse transcription PCR (RT-PCR) kit, and a microarray kit.
  • PCR polymerase chain reaction
  • RT-PCR reverse transcription PCR
  • the kit of the present invention may optionally include reagents necessary for PCR amplification, such as buffer, DNA polymerase, DNA polymerase cofactor, and dNTPs.
  • reagents necessary for PCR amplification such as buffer, DNA polymerase, DNA polymerase cofactor, and dNTPs.
  • the kit according to the present invention can be manufactured in a number of separate packaging or compartments containing the above-mentioned reagent components, and the kit according to the present invention is a diagnostic kit containing the essential elements required to perform DNA or RNA chipping. It can be.
  • Another aspect of the present invention is a) hsa-miR-1273c, hsa-miR-142-3p, hsa-miR-142-5p, hsa-miR-144-3p, hsa-miR-150 in a biological sample isolated from a subject.
  • Step a) is a process of collecting a biological sample from an individual who needs to be tested for diagnosis or prognosis of interstitial cystitis and measuring the expression level of miRNA in the sample.
  • the miRNA in step a) may be single or a combination of two or more.
  • the subject in step a) may be an individual with suspected symptoms of interstitial cystitis or a patient with interstitial cystitis.
  • the biological sample in step a) may be one or more selected from the group consisting of whole blood, plasma, serum, lymph, saliva, urine, and tissue.
  • the level of miRNA expression in the present invention can be measured without limitation based on conventional RNA expression analysis methods.
  • the gene expression level in step a) is determined by next-generation sequencing (NGS), polymerase chain reaction (PCR), reverse transcription-polymerase chain reaction (RT-PCR), competitive RT-PCR, It may be measured by one or more methods selected from the group consisting of real-time PCR, real-time RT-PCR, nuclease protection assay, in situ hybridization, DNA microarray, and Northern blot.
  • NGS next-generation sequencing
  • PCR polymerase chain reaction
  • RT-PCR reverse transcription-polymerase chain reaction
  • competitive RT-PCR it may be measured by one or more methods selected from the group consisting of real-time PCR, real-time RT-PCR, nuclease protection assay, in situ hybridization, DNA microarray, and Northern blot.
  • step a) is performed on hsa-miR-1273c, hsa-miR-142-3p, hsa-miR-142-5p, hsa-miR-144-3p in biological samples isolated from the subject.
  • hsa-miR-150-5p hsa-miR-185-5p, hsa-miR-3934-5p
  • hsa-miR-6126 hsa-miR-8485, hsa-let-7d-3p
  • hsa-miR-10a -3p hsa-miR-30d-5p
  • hsa-miR-374b-5p hsa-miR-423-3p
  • hsa-miR-532-3p hsa-miR-874-3p. It may be measuring the expression level.
  • Step b) is a process of predicting whether the subject will progress to interstitial cystitis or the prognosis for interstitial cystitis treatment based on the level of miRNA expression measured in the biological sample.
  • the normal control group in step b) may be an individual who has no symptoms suspected of interstitial cystitis or has not been diagnosed with interstitial cystitis, or a biological sample obtained therefrom.
  • step b) may be to diagnose interstitial cystitis when the subject's miRNA expression level is higher or lower than that of the normal control group based on fc according to statistical analysis.
  • step b) is performed in subjects compared to normal controls.
  • the present invention can provide compositions and kits for diagnosing interstitial cystitis or predicting prognosis by discovering new biomarkers that can diagnose interstitial cystitis or predict prognosis of interstitial cystitis. Furthermore, it is possible to provide compositions and kits for diagnosing interstitial cystitis or predicting prognosis, and further improves interstitial cystitis, such as drug responsiveness and recurrence of patients. By quickly and accurately diagnosing the treatment prognosis of cystitis, we can provide treatment tailored to the patient's condition.
  • the interstitial cystitis patient group was selected as adults who had symptoms of bladder pain, urgency, and frequent urination for at least 6 months before participating in the experiment, and had pain of 4 or more out of 10 on the VAS (visual analog scale). In addition, within 2 months before participating in the experiment, there was a history of endoscopic treatment due to findings of a Hunter lesion through cystoscopy.
  • Urine was collected by inserting a catheter into the urethra and centrifuged at 2,500 rpm at 4°C for 20 minutes. The supernatant was transferred to a new tube and stored at -80°C until exosomes were isolated.
  • Urinary exosomes were isolated using an aqueous two-phase system (Exo2D, EsosomePlus) according to the manufacturer's instructions. Briefly, samples were thawed at 4°C and then centrifuged at 2,500 rpm for 5 minutes to remove remaining cell debris. And to separate exosomes, 10 mL of supernatant was transferred to a 15 mL tube. Afterwards, 2 mL of Exo2D reagent B was added to the purified urine, and the mixture was incubated at 4°C for 30 minutes. Precipitated exosomes were recovered by centrifugation at 3000 ⁇ g, 4°C for 30 minutes. The exosome pellet was resuspended in 200 ⁇ L of phosphate-buffered saline (PBS).
  • PBS phosphate-buffered saline
  • RNA isolated from each sample was used to construct a sequencing library with the SMARTer smRNA-Seq Kit (for Illumina) according to the manufacturer's protocol. Briefly, the input RNA was first polyadenylated to provide an initial sequence for the oligo-(dT) primer. cDNA synthesis was performed by a 3' smRNA dT Primer containing an adapter sequence at the 5' end of each first-strand cDNA molecule. Once the MMLV-derived PrimeScriptTM Reverse Transcriptase (RT) reaches the 5' end of each RNA template, non-template nucleotides are bound by SMART smRNA Oligo enhanced with locked nucleic acid (LNA) technology for greater sensitivity.
  • LNA locked nucleic acid
  • templated nucleotide was added.
  • PrimeScript RT used SMART smRNA Oligo as a template to add a second adapter sequence to the 3' end of each first-strand cDNA molecule.
  • full-length Illumina adapters (including the index sequence for sample multiplexing) were added during PCR amplification.
  • the forward PCR primer was bound to the sequence added by SMART smRNA Oligo, and the reverse PCR primer was bound to the sequence added by 3' smRNA dT Primer.
  • the resulting library cDNA molecules contained the sequences required for clustering in an Illumina flow cell.
  • the library was verified for size, purity, and concentration on an Agilent Bioanalyzer.
  • the library was pooled in equimolar amounts and sequenced with an Illumina HiSeq 2500 equipment, and 51 base reads were generated. Image decomposition and quality value calculation were performed using modules of the Illumina pipeline.
  • smRNA expression was quantified and differentially expressed smRNAs were filtered.
  • the raw sequence reads obtained from sequencing were filtered according to quality.
  • Adapter sequences were cut from the raw sequence reads.
  • One cluster was formed with trimmed reads and non-adapter reads.
  • Clusters contained reads that exactly matched sequence characteristics as well as read length, and were assigned a temporary cluster ID and the number of reads held in the cluster. To effectively remove large amounts of rRNA, reads were aligned to the rRNA sequence and removed.
  • RNAcentral 14.0 non-coding RNA database
  • Example 2 Selection of biomarkers for diagnosing or predicting prognosis of interstitial cystitis
  • miRNAs were differentially expressed in the interstitial cystitis patient group compared to the normal control group, of which 8 were upregulated (hsa-miR-142-3p, hsa-miR-142- 5p, hsa-miR-150-5p, hsa-miR-16-5p, hsa-miR-185-5p, hsa-miR-31-5p, hsa-miR-6126, and hsa-miR-941) and 22 downstream.
  • 8 were upregulated (hsa-miR-142-3p, hsa-miR-142- 5p, hsa-miR-150-5p, hsa-miR-16-5p, hsa-miR-185-5p, hsa-miR-31-5p, hsa-miR-6126, and hsa-miR-941) and 22 downstream.
  • miRNAs were differentially expressed in the interstitial cystitis patient group compared to the normal control group, of which 9 were upregulated (hsa-miR-1273c, hsa-miR-142-3p, hsa-miR-142-5p, hsa-miR-144-3p, hsa-miR-150-5p, hsa-miR-185-5p, hsa-miR-3934-5p, hsa-miR-6126 and hsa-miR- 8485) and 7 downregulated miRNAs (hsa-let-7d-3p, hsa-miR-10a-3p, hsa-miR-30d-5p, hsa-miR-374b-5p, hsa-miR-423-3p, hsa-miR-532-3p and hsa-miR-874-3p)

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Abstract

La présente invention concerne un nouveau biomarqueur pour le diagnostic ou la prédiction de pronostic de la cystite interstitielle et son utilisation. En identifiant un biomarqueur qui permet le diagnostic ou le pronostic de la cystite interstitielle, il est possible de fournir une composition et un kit pour le diagnostic ou le pronostic de la cystite interstitielle. En outre, le biomarqueur peut déterminer rapidement et avec précision le pronostic thérapeutique de la cystite interstitielle, comme la réactivité aux médicaments et la récidive, ce qui permet de proposer des traitements sur mesure en fonction de l'état du patient.
PCT/KR2023/020158 2022-12-16 2023-12-08 Nouveaux biomarqueurs pour le diagnostic ou le pronostic de la cystite interstitielle et leur utilisation Ceased WO2024128688A1 (fr)

Applications Claiming Priority (4)

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KR20220176747 2022-12-16
KR10-2022-0176747 2022-12-16
KR1020230169219A KR20240097996A (ko) 2022-12-16 2023-11-29 간질성방광염 진단 또는 예후 예측용 신규 바이오마커 및 이의 용도
KR10-2023-0169219 2023-11-29

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Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106555003A (zh) * 2016-11-25 2017-04-05 南京拓睿谱基因科技有限公司 腺性膀胱炎和膀胱癌诊断区分标志物、诊断试剂或试剂盒

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106555003A (zh) * 2016-11-25 2017-04-05 南京拓睿谱基因科技有限公司 腺性膀胱炎和膀胱癌诊断区分标志物、诊断试剂或试剂盒

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
ARAI TAKAYUKI; FUSE MIKI; GOTO YUSUKE; KAGA KANYA; KUROZUMI AKIRA; YAMADA YASUTAKA; SUGAWARA SHO; OKATO ATSUSHI; ICHIKAWA TOMOHIKO: "Molecular pathogenesis of interstitial cystitis based on microRNA expression signature:miR-320family-regulated molecular pathways and targets", JOURNAL OF HUMAN GENETICS, SPRINGER SINGAPORE, SINGAPORE, vol. 63, no. 5, 12 March 2018 (2018-03-12), Singapore, pages 543 - 554, XP036487961, ISSN: 1434-5161, DOI: 10.1038/s10038-018-0419-x *
GHEINANI ALI HASHEMI, AKSHAY AKSHAY, BESIC MUSTAFA, KUHN ANNETTE, KELLER IRENE, BRUGGMANN RÉMY, REHRAUER HUBERT, ADAM ROSALYN M., : "Integrated mRNA-miRNA transcriptome analysis of bladder biopsies from patients with bladder pain syndrome identifies signaling alterations contributing to the disease pathogenesis", BMC UROLOGY, BIOMED CENTRAL, LONDON, GB, vol. 21, no. 1, 1 December 2021 (2021-12-01), GB , pages 172, XP093181913, ISSN: 1471-2490, DOI: 10.1186/s12894-021-00934-0 *
URABE FUMIHIKO, FURUTA AKIRA, IGARASHI TARO, SUZUKI YASUYUKI, EGAWA SHIN, KIMURA TAKAHIRO: "Urinary extracellular vesicle microRNA profiling for detection in patients with interstitial cystitis", TRANSLATIONAL ANDROLOGY AND UROLOGY, vol. 11, no. 7, 1 July 2022 (2022-07-01), pages 1063 - 1066, XP093181916, ISSN: 2223-4683, DOI: 10.21037/tau-22-240 *
VERONICA SANCHEZ FREIRE, FIONA C. BURKHARD, THOMAS M. KESSLER, ANNETTE KUHN, ANNETTE DRAEGER, KATIA MONASTYRSKAYA: "MicroRNAs May Mediate the Down-Regulation of Neurokinin-1 Receptor in Chronic Bladder Pain Syndrome", THE AMERICAN JOURNAL OF PATHOLOGY, ELSEVIER INC., US, vol. 176, no. 1, 1 January 2010 (2010-01-01), US , pages 288 - 303, XP055726306, ISSN: 0002-9440, DOI: 10.2353/ajpath.2010.090552 *

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