Decoding the Role of DVL1 in Intracranial Meningioma
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 progressio...
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2021
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oai:doaj.org-article:8d63e4e9d8984431aa78cd508119c9ee2021-11-11T17:24:49ZDecoding the Role of DVL1 in Intracranial Meningioma10.3390/ijms2221119961422-00671661-6596https://doaj.org/article/8d63e4e9d8984431aa78cd508119c9ee2021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11996https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067In 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 <i>DVL1</i> 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 (<i>p</i> = 0.029) and a higher meningioma grade (<i>p</i> = 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.Anja BukovacKatarina DragičevićAnja KafkaDarko OreškovićSanja Cesarec-AugustinovićNives Pećina-ŠlausMDPI AGarticleDVL1PDZ domainβ-cateninWnt signaling pathwayintracranial meningiomaBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11996, p 11996 (2021) |
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| collection |
DOAJ |
| language |
EN |
| topic |
DVL1 PDZ domain β-catenin Wnt signaling pathway intracranial meningioma Biology (General) QH301-705.5 Chemistry QD1-999 |
| spellingShingle |
DVL1 PDZ domain β-catenin Wnt signaling pathway intracranial meningioma Biology (General) QH301-705.5 Chemistry QD1-999 Anja Bukovac Katarina Dragičević Anja Kafka Darko Orešković Sanja Cesarec-Augustinović Nives Pećina-Šlaus Decoding the Role of DVL1 in Intracranial Meningioma |
| description |
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 <i>DVL1</i> 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 (<i>p</i> = 0.029) and a higher meningioma grade (<i>p</i> = 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. |
| format |
article |
| author |
Anja Bukovac Katarina Dragičević Anja Kafka Darko Orešković Sanja Cesarec-Augustinović Nives Pećina-Šlaus |
| author_facet |
Anja Bukovac Katarina Dragičević Anja Kafka Darko Orešković Sanja Cesarec-Augustinović Nives Pećina-Šlaus |
| author_sort |
Anja Bukovac |
| title |
Decoding the Role of DVL1 in Intracranial Meningioma |
| title_short |
Decoding the Role of DVL1 in Intracranial Meningioma |
| title_full |
Decoding the Role of DVL1 in Intracranial Meningioma |
| title_fullStr |
Decoding the Role of DVL1 in Intracranial Meningioma |
| title_full_unstemmed |
Decoding the Role of DVL1 in Intracranial Meningioma |
| title_sort |
decoding the role of dvl1 in intracranial meningioma |
| publisher |
MDPI AG |
| publishDate |
2021 |
| url |
https://doaj.org/article/8d63e4e9d8984431aa78cd508119c9ee |
| work_keys_str_mv |
AT anjabukovac decodingtheroleofdvl1inintracranialmeningioma AT katarinadragicevic decodingtheroleofdvl1inintracranialmeningioma AT anjakafka decodingtheroleofdvl1inintracranialmeningioma AT darkooreskovic decodingtheroleofdvl1inintracranialmeningioma AT sanjacesarecaugustinovic decodingtheroleofdvl1inintracranialmeningioma AT nivespecinaslaus decodingtheroleofdvl1inintracranialmeningioma |
| _version_ |
1718432130181103616 |