nach oben

Irish Journal of Medical Science (1971 -)

Erschienen in:

06.09.2024 | Original Article

Identification of potential miRNA-mRNA regulatory network contributing to pathogenesis of polycystic ovarian syndrome

verfasst von: Prajna Bhandary, Dhananjay B. Alagundagi, Prasanna Kumar Shetty, Prakash Patil

Erschienen in: Irish Journal of Medical Science (1971 -) | Ausgabe 6/2024

Einloggen, um Zugang zu erhalten

Abstract

Background

Polycystic ovarian syndrome (PCOS), a gynae-endocrine disorder, has a relatively high risk of differential expression of miRNA (DE-miRNA) in the disease progression.

Aims

To identify the DE-miRNA in the progression of PCOS in the ovarian cumulus cells.

Methods

The microarray dataset GSE72274 was analysed for PCOS-associated DE-miRNAs. miRNet identifies the target genes. Protein–protein interaction (PPI) network was constructed and hub genes were analysed by topology and module analysis. Transcription factors (TFs) and protein kinases (PKs) regulating the hub genes were identified using X2K tool. Biological functions were analysed using DAVID software. Finally, the DGIdb drug-gene interaction tool identifies the candidate medications.

Results

A total of 1577 DE-miRNAs linked to PCOS were identified, with 13 meeting the specified criteria. Subsequently, its 2053 target genes were retrieved through miRNet. Topology and module analysis identified the hub genes VEGFA, SOX2, KRAS, AKT1, and SMAD4 that are implicated in ovarian regulation. Notably, the study highlighted the significant role of the wnt signalling pathway, which is involved in ovarian function, specifically in follicle development, corpus luteum formation, and steroid production. Additionally, six TFs and PKs were identified as important regulators of these hub genes, and the potential medication interactions identified 11 medicines for VEGFA, KRAS, AKT1, and SMAD4 genes, while no suitable drug for SOX2 was identified.

Conclusion

Identified, hub genes are known to associate with the regulation of ovarian function such as oocyte development, and steroid synthesis via the wnt signalling pathway.

Nur mit Berechtigung zugänglich

Huo Y, Ji S, Yang H et al (2022) Differential expression of microRNA in the serum of patients with polycystic ovary syndrome with insulin resistance. Ann Transl Med 10:762–762. https://doi.org/10.21037/ATM-22-2941CrossRefPubMedPubMedCentral

AE Butler, V Ramachandran, S Hayat, SR Dargham, TK Cunningham, M Benurwar, T Sathyapalan, SH Najafi-Shoushtari, SL Atkin (2019) Expression of microRNA in follicular fluid in women with and without PCOS. Sci Rep 9. https://doi.org/10.1038/S41598-019-52856-5.

Q Shen, M Chen, X Zhao, Y Liu, … XR-S (2020) biology in, undefined 2020, Versican expression level in cumulus cells is associated with human oocyte developmental competence, Taylor Fr. Shen, M Chen, X Zhao, Y Liu, X Ren, L ZhangSystems Biol Reprod Med 2020 Taylor Fr. 66:176–184. https://doi.org/10.1080/19396368.2020.1725685

G Rashid, NA Khan, D Elsori, RA Youness, H Hassan, D Siwan, N Seth, MA Kamal, S Rizvi, AM Babker, W Hafez (2024) miRNA expression in PCOS: unveiling a paradigm shift toward biomarker discovery. Arch Gynecol Obstet 1–17. https://doi.org/10.1007/S00404-024-07379-4/METRICS

Chen HX, Fu YF, Guo ZX, Zhou XD (2022) MicroRNA-29c-3p participates in insulin function to modulate polycystic ovary syndrome via targeting Forkhead box O 3. Bioengineered 13:4361–4371. https://doi.org/10.1080/21655979.2022.2033014CrossRefPubMedPubMedCentral

Butler AE, Ramachandran V, Hayat S et al (2019) Expression of microRNA in follicular fluid in women with and without PCOS. Sci Rep 9:1–9. https://doi.org/10.1038/s41598-019-52856-5CrossRef

L Mu, X Sun, M Tu, D Zhang (2021) Non-coding RNAs in polycystic ovary syndrome: a systematic review and meta-analysis. Reprod Biol Endocrinol 19. https://doi.org/10.1186/S12958-020-00687-9

Bhandary P, Shetty PK, Manjeera L, Patil P (2022) Hormonal, genetic, epigenetic and environmental aspects of polycystic ovarian syndrome. Gene Reports 29:101698. https://doi.org/10.1016/J.GENREP.2022.101698CrossRef

Y Xuan Wu, Y Shan Lin, S Chen Li, X Yao, M Cheng, L Zhu, H Ying Liu (2021) microRNA-194 is increased in polycystic ovary syndrome granulosa cell and induces KGN cells apoptosis by direct targeting heparin-binding EGF-like growth factor. Reprod Biol Endocrinol 19. https://doi.org/10.1186/S12958-021-00850-W

10.

Alexandri C, Daniel A, Bruylants G, Demeestere I (2020) The role of microRNAs in ovarian function and the transition toward novel therapeutic strategies in fertility preservation: from bench to future clinical application. Hum Reprod Update 26:174–196. https://doi.org/10.1093/HUMUPD/DMZ039CrossRefPubMed

11.

Turathum B, Gao E-M, Chian R-C, Jessus C (2021) The function of cumulus cells in oocyte growth and maturation and in subsequent ovulation and fertilization. Mdpi Com. https://doi.org/10.3390/cells10092292CrossRef

12.

Chang L, Xia J (2023) MicroRNA regulatory network analysis using miRNet 2.0. Methods Mol Biol 2594:185–204. https://doi.org/10.1007/978-1-0716-2815-7_14CrossRefPubMed

13.

Szklarczyk D, Gable AL, Lyon D et al (2019) STRING v11: protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. Nucleic Acids Res 47:D607–D613. https://doi.org/10.1093/NAR/GKY1131CrossRefPubMed

14.

Zhou F, Xing Y, Cheng T et al (2022) Exploration of hub genes involved in PCOS using biological informatics methods. Med (United States) 101:E30905. https://doi.org/10.1097/MD.0000000000030905CrossRef

15.

Clarke DJB, Kuleshov MV, Schilder BM et al (2018) eXpression2Kinases (X2K) Web: linking expression signatures to upstream cell signalling networks. Nucleic Acids Res 46:W171–W179. https://doi.org/10.1093/NAR/GKY458CrossRefPubMedPubMedCentral

16.

Sherman BT, Hao M, Qiu J et al (2022) DAVID: a web server for functional enrichment analysis and functional annotation of gene lists (2021 update). Nucleic Acids Res 50:W216–W221. https://doi.org/10.1093/NAR/GKAC194CrossRefPubMedPubMedCentral

17.

Cannon M, Stevenson J, Stahl K et al (2024) DGIdb 50: rebuilding the drug-gene interaction database for precision medicine and drug discovery platforms. Nucleic Acids Res 52:D1227–D1235. https://doi.org/10.1093/NAR/GKAD1040CrossRefPubMed

18.

R Li, Y Yu, SO Jaafar, B Baghchi, M Farsimadan, I Arabipour, H Vaziri (2022) Genetic variants miR-126, miR-146a, miR-196a2, and miR-499 in polycystic ovary syndrome. Br J Biomed Sci 79. https://doi.org/10.3389/BJBS.2021.10209/FULL

19.

Sepahi N, Kohan L, Jahromi AR et al (2017) mir-126 rs4636297 and TGFβRI rs334348 functional gene variants are associated with susceptibility to endometriosis and its severity. Gynecol Endocrinol 33:429–432. https://doi.org/10.1080/09513590.2017.1290064CrossRefPubMed

20.

X Jiang, J Li, B Zhang, J Hu, J Ma, L Cui, ZC-F and sterility, undefined 2021, Differential expression profile of plasma exosomal microRNAs in women with polycystic ovary syndrome, Elsevier. (n.d.). https://www.sciencedirect.com/science/article/pii/S0015028220307731 (accessed March 30, 2024)

21.

Li C, Chen Y, Chen X et al (2020) MicroRNA-183-5p is stress-inducible and protects neurons against cell death in amyotrophic lateral sclerosis. J Cell Mol Med 24:8614–8622. https://doi.org/10.1111/JCMM.15490CrossRefPubMedPubMedCentral

22.

I Ischenko, M Rao, J Li, MJ Hayman, S Powers, O Petrenko, NC Reich (n.d.) KRAS drives immune evasion in a genetic model of pancreatic cancer, Nature.ComI Ischenko, S D’Amico, M Rao, J Li, MJ Hayman, S Powers, O Petrenko, NC ReichNature Commun. 2021•nature.Com. https://doi.org/10.1038/s41467-021-21736-w

23.

ABMMK Islam, E Mohammad, MAAK Khan (2020) Aberration of the modulatory functions of intronic microRNA hsa-miR-933 on its host gene ATF2 results in type II diabetes mellitus and neurodegenerative disease development, Hum. Genomics. 14. https://doi.org/10.1186/S40246-020-00285-1

24.

Qin Y, Wang Y, Zhao H et al (2021) Aberrant miRNA-mRNA regulatory network in polycystic ovary syndrome is associated with markers of insulin sensitivity and inflammation. Ann Transl Med 9:1405–1405. https://doi.org/10.21037/ATM-21-1288CrossRefPubMedPubMedCentral

25.

Y Yang, YC-S in cancer biology, undefined 2022, The impact of VEGF on cancer metastasis and systemic disease, Elsevier Yang, Y CaoSeminars Cancer Biol. 2022•Elsevier. (n.d.). https://www.sciencedirect.com/science/article/pii/S1044579X22000670 (accessed April 1, 2024)

26.

A White (2023) GB- Biomolecules, undefined 2023, VEGFA isoforms as pro-angiogenic therapeutics for cerebrovascular diseases, Mdpi.Comal White, GJ BixBiomolecules, 2023•mdpi.Com. https://doi.org/10.3390/biom13040702

27.

M Huang, Y Ji, J Chen, D Li, T Zhou, … PQ-AP, undefined 2023, Targeted VEGFA therapy in regulating early acute kidney injury and late fibrosis, Nature.ComM Huang, Y Ji, J Chen, D Li, T Zhou, P Qi, X Wang, X Li, Y Zhang, X Yu, L Wu, X Sun, G CaiActa Pharmacol. Sin. 2023•nature.Com. (n.d.). https://www.nature.com/articles/s41401-023-01070-1 (accessed August 10, 2024)

28.

Wan R, Feng J, Tang L (2021) Consequences of mutations and abnormal expression of smad4 in tumours and t cells. Onco Targets Ther 14:2531–2540. https://doi.org/10.2147/OTT.S297855CrossRefPubMedPubMedCentral

29.

Y Zhou, Y Wu, C Chong, S Zhong, ZW- Heliyon, undefined 2023, Irpex lacteus polysaccharide exhibits therapeutic potential for ovarian fibrosis in PCOS rats via the TGF-β1/smad pathway, Cell.ComYY Zhou, YQ Wu, CJ Chong, SM Zhong, ZX Wang, XH Qin, ZQ Liu, JY Liu, JL SongHeliyon, 2023•cell.Com. (n.d.). https://www.cell.com/heliyon/pdf/S2405-8440(23)05949-2.pdf (accessed April 1, 2024)

30.

YH Kim, SW Choe, MY Chae, S Hong, SP Oh (2018) SMAD4 deficiency leads to development of arteriovenous malformations in neonatal and adult mice. J Am Heart Assoc 7. https://doi.org/10.1161/JAHA.118.009514

31.

MA Moga, A Bălan, OG Dimienescu, V Burtea, RM Dragomir, CV Anastasiu (2019) Circulating miRNAs as biomarkers for endometriosis and endometriosis-related ovarian cancer—an overview. J Clin Med 8. https://doi.org/10.3390/JCM8050735

32.

S Elsherif, S Faria, C Lall, … RI-J of computer, undefined 2019, Ovarian cancer genetics and implications for imaging and therapy, Journals.Lww.ComSB Elsherif, SC Faria, C Lall, R Iyer, PR BhosaleJournal Comput. Assist. Tomogr. 2019•journals.Lww.Com. (n.d.). https://journals.lww.com/jcat/fulltext/2019/11000/Ovarian_Cancer_Genetics_and_Implications_for.2.aspx (accessed April 1, 2024)

33.

Yan MQ, Zhu BH, Liu XH et al (2023) Mitoguardin 1 and 2 promote granulosa cell proliferation by activating AKT and regulating the Hippo-YAP1 signaling pathway. Cell Death Dis 14:1–12. https://doi.org/10.1038/s41419-023-06312-yCrossRef

34.

A Alwhaibi, A Verma, M Adil, PS-P research, undefined 2019, The unconventional role of Akt1 in the advanced cancers and in diabetes-promoted carcinogenesis, ElsevierA Alwhaibi, A Verma, MS Adil, PR SomanathPharmacological Res. 2019•Elsevier. (n.d.). https://www.sciencedirect.com/science/article/pii/S1043661818318991 (accessed April 1, 2024)

35.

Chen J, Somanath PR, Razorenova O et al (2005) Akt1 regulates pathological angiogenesis, vascular maturation and permeability in vivo. Nat Med 11:1188–1196. https://doi.org/10.1038/nm1307CrossRefPubMedPubMedCentral

36.

T Schaefer, CL- Oncogene, undefined 2020, SOX2 protein biochemistry in stemness, reprogramming, and cancer: the PI3K/AKT/SOX2 axis and beyond, Nature.ComT Schaefer, C LengerkeOncogene, 2020•nature.Com. (n.d.). https://www.nature.com/articles/s41388-019-0997-x (accessed April 1, 2024)

37.

G Maurizi, N Verma, A Gadi, A Mansukhani, CB- Oncogene, undefined 2018, Sox2 is required for tumor development and cancer cell proliferation in osteosarcoma, Nature.ComG Maurizi, N Verma, A Gadi, A Mansukhani, C BasilicoOncogene, 2018•nature.Com. (n.d.). https://www.nature.com/articles/s41388-018-0292-2 (accessed August 10, 2024)

38.

D Yuan, J Luo, Y Sun, L Hao, J Zheng, ZY-C Signalling, undefined 2021, PCOS follicular fluid derived exosomal miR-424–5p induces granulosa cells senescence by targeting CDCA4 expression, ElsevierD Yuan, J Luo, Y Sun, L Hao, J Zheng, Z YangCellular Signalling, 2021•Elsevier. (n.d.). https://www.sciencedirect.com/science/article/pii/S0898656821001194 (accessed April 20, 2024)

39.

JG- Reproduction, undefined 2015, The role of WNT signaling in adult ovarian folliculogenesis, Rep.Bioscientifica.ComJAH GiffordReproduction, 2015•rep.Bioscientifica.Com. (n.d.). https://rep.bioscientifica.com/view/journals/rep/150/4/R137.xml (accessed April 29, 2024)

40.

Zhu M, Fan Z (2022) The role of the Wnt signalling pathway in the energy metabolism of bone remodelling. Cell Prolif 55:e13309. https://doi.org/10.1111/CPR.13309CrossRefPubMedPubMedCentral

41.

O Habara, C Logan, … MK-A-, undefined 2021, WNT signaling in pre-granulosa cells is required for ovarian folliculogenesis and female fertility, Journals.Biologists.ComO Habar. CY Logan, M Kanai-Azuma, R Nusse, HM Tak. 2021•journals.Biologists.Com. (n.d.). https://journals.biologists.com/dev/article-abstract/148/9/dev198846/261700 (accessed September 13, 2023)

42.

L Li, X Shi, Y Shi, Z Wang (2021) The signaling pathways involved in ovarian follicle development. Front Physiol 12. https://doi.org/10.3389/FPHYS.2021.730196/FULL

Titel: Identification of potential miRNA-mRNA regulatory network contributing to pathogenesis of polycystic ovarian syndrome
verfasst von: Prajna Bhandary
Dhananjay B. Alagundagi
Prasanna Kumar Shetty
Prakash Patil
Publikationsdatum: 06.09.2024
Verlag: Springer International Publishing
Erschienen in: Irish Journal of Medical Science (1971 -) / Ausgabe 6/2024
Print ISSN: 0021-1265
Elektronische ISSN: 1863-4362
DOI: https://doi.org/10.1007/s11845-024-03795-2

Gamma gap as a prognostic marker of treatment response in patients with multiple myeloma

Original Article

Evaluation of neutrophil activation marker in patients with vitiligo

Open Access
Original Article

Effects of early mobilization in elderly patients undergoing cardiac surgery

Original Article

D-dimer/high sensitive troponin I ratio is useful in predicting in-hospital mortality in pulmonary embolism patients

Open Access
Original Article

An exploration of fibre intake and bowel function in a sample of adults at an Irish university campus

Open Access
Original Article

An investigation into General Practitioners’ experience with Long Covid

Open Access
Original Article

Kompaktes Leitlinien-Wissen Innere Medizin (Link öffnet in neuem Fenster)

Mit medbee Pocketcards schnell und sicher entscheiden.
Leitlinien-Wissen kostenlos und immer griffbereit auf ihrem Desktop, Handy oder Tablet.

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

Verbände und Cremes gegen Dekubitus: „Wir wissen nicht, was sie bringen!“

17.01.2025
Dekubitus
Nachrichten

Die Datenlage zur Wirksamkeit von Verbänden oder topischen Mitteln zur Prävention von Druckgeschwüren sei schlecht, so die Verfasser einer aktuellen Cochrane-Studie. Letztlich bleibe es unsicher, ob solche Maßnahmen den Betroffenen nutzen oder schaden.

Schützt das tägliche Glas Milch vor Darmkrebs?

17.01.2025
Kolorektales Karzinom
Nachrichten

Die Milch machts – sie bietet Frauen nach Daten einer großen Ernährungsanalyse den besten Darmkrebsschutz aller Lebensmittel, was am hohen Kalziumgehalt liegen dürfte. Am anderen Ende des Spektrums steht der Alkoholkonsum: Das Glas Wein am Abend ist eher ungünstig.

Vorsicht mit Glukokortikoiden bei Glomerulopathie

16.01.2025
Primäre Glomerulonephritiden
Nachrichten

Auch niedrig dosierte Glukokortikoide zur Behandlung einer primären Glomerulopathie lassen offenbar die Infektionsgefahr steigen. In einer US-Studie hing das Risiko vor allem mit der kombinierten Anwendung von Immunsuppressiva zusammen.

KI-gestütztes Mammografiescreening überzeugt im Praxistest

16.01.2025
Künstliche Intelligenz im Gesundheitswesen
Nachrichten

Mit dem Einsatz künstlicher Intelligenz lässt sich die Detektionsrate im Mammografiescreening offenbar deutlich steigern. Mehr unnötige Zusatzuntersuchungen sind laut der Studie aus Deutschland nicht zu befürchten.

EKG Essentials: EKG befunden mit System (Link öffnet in neuem Fenster)

In diesem CME-Kurs können Sie Ihr Wissen zur EKG-Befundung anhand von zwölf Video-Tutorials auffrischen und 10 CME-Punkte sammeln.
Praxisnah, relevant und mit vielen Tipps & Tricks vom Profi.

Jetzt 10 CME-Punkte sammeln

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Identification of potential miRNA-mRNA regulatory network contributing to pathogenesis of polycystic ovarian syndrome