Decoding the Role of DVL1 in Intracranial Meningioma

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• Autor: Anja Bukovac
• Autor: Katarina Dragičević
• Autor: Anja Kafka
• Autor: Darko Orešković
• Autor: Sanja Cesarec-Augustinović
• Autor: Nives Pećina-Šlaus
• Autorova ustanova: Sveučilište u Zagrebu; Medicinski fakultet; (HRVATSKI INSTITUT ZA ISTRAŽIVANJE MOZGA)
• Autorova ustanova: Sveučilište u Zagrebu; Medicinski fakultet; (KATEDRA ZA MEDICINSKU BIOLOGIJU)
• Znanstveno / umjetničko područje, polje i grana: BIOMEDICINA I ZDRAVSTVO; Temeljne medicinske znanosti; Neuroznanost
• Znanstveno / umjetničko područje, polje i grana: BIOMEDICINA I ZDRAVSTVO; Temeljne medicinske znanosti

Sažetak (engleski)

In the search for molecular candidates for targeted meningioma therapies, increasing attention has been paid to the role of signaling pathways in the development and progression of intracranial meningiomas. Although it is well known that the Wnt signaling pathway is involved in meningioma progression, the role of its central mediator, DVL1, is still unclear. In order to investigate the influence of DVL1 gene alterations on the progression of human intracranial meningioma, we focused on its central PDZ domain, which is responsible for DVL interaction with the Fzd receptor and the phosphorylation of DVL mediated through the casein kinases CK1 and CK2. A genetic analysis of genomic instability revealed the existence of microsatellite instability in 9.09% and the loss of heterozygosity in 6.06% of the samples. The sequencing of the PDZ gene region showed repetitive deletions of two bases located in intron 7 and exon 8, and a duplication in intron 8 in most samples, with different outcomes on the biological function of the DVL1 protein. Immunohistochemistry revealed that the nuclear expression of DVL1 was significantly correlated with a higher expression of active β-catenin (p = 0.029) and a higher meningioma grade (p = 0.030), which leads to the conclusion that it could be used as biomarker for meningioma progression and the activation of the Wnt signaling pathway.

• Ključne riječi (engleski): Adult; Aged; Aged, 80 and over; Biomarkers, Tumor / genetics; Biomarkers, Tumor / metabolism; Dishevelled Proteins / genetics*; Dishevelled Proteins / metabolism; Female; Humans; Male; Meningeal Neoplasms / genetics; Meningeal Neoplasms / metabolism; Meningeal Neoplasms / pathology; Meningioma / genetics*; Meningioma / metabolism; Meningioma / pathology; Microsatellite Instability; Middle Aged; Mutation; PDZ Domains; Prognosis; Young Adult; beta Catenin / genetics; beta Catenin / metabolism
• Jezik: engleski
• Vrsta publikacije: Znanstveni rad - Izvorni znanstveni rad
• Status objave: Objavljen
• Vrsta recenzije: Recenziran
• Verzija publikacije: Objavljena verzija rada (izdavačev PDF)
• Naslov časopisa: International Journal of Molecular Sciences
• Brojčani podaci: vol. 22, br. 21, 11996
• e-ISSN: 1422-0067
• DOI: https://doi.org/10.3390/ijms222111996
• URN:NBN: urn:nbn:hr:105:542236
• Datum objave publikacije: 2021-11-05
• URL dokumenta: https://www.mdpi.com/1422-0067/22/21/11996
• Vrsta resursa: Tekst
• Prava pristupa: Otvoreni pristup
• Datum i vrijeme pohrane: 2022-03-11 09:38:14