ArticleCancer cell international2021
The loss of DLG2 isoform 7/8, but not isoform 2, is critical in advanced staged neuroblastoma.
Article in Cancer cell international, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 9 citations in OpenAlex.
- The Physiological and Pathological Mechanisms of LIN2, LIN7, LIN10 and Their Tripartite Complex.Journal of cellular and molecular medicine · 2025Review
- Identification and verification of international neuroblastoma staging system (INSS) stage-related genes as potential biomarkers for neuroblastoma prognostic models.Frontiers in cell and developmental biology · 2025Article
- Review
- Bioinformatics analysis of miRNAs in the neuroblastoma 11q-deleted region reveals a role of miR-548l in both 11q-deleted and MYCN amplified tumour cells.Scientific reports · 2022Article
- Inflammation suppresses DLG2 expression decreasing inflammasome formation.Journal of cancer research and clinical oncology · 2022Article
- Deciphering the Heterogeneity of the Internal Environment of Hippocampal Neurons during Maturation by Raman Spectroscopy.ACS omega · 2022Article
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundNeuroblastoma is a childhood neural crest tumor showing large clinical and genetic heterogeneity, one form displaying 11q-deletion is very aggressive. It has been shown that 11q-deletion results in decreased expression of DLG2, a gene residing in the deleted region. DLG2 has a number of different isoforms with the main difference is the presence or absence of a L27 domain. The L27 domain containing DLG proteins can form complexes with CASK/MPP and LIN7 protein family members, which will control cell polarity and signaling.
methodsWe evaluated the DLG gene family and the LIN7 gene family for their expression in differently INSS staged neuroblastoma from publically available data and primary tumors, we included two distinct DLG1 and DLG2 N-terminal transcript isoforms encoding L27 domains for their expression. Functionality of DLG2 isoforms and of LIN7A were evaluated in the 11q-deleted neuroblastoma cell line SKNAS.
resultsIn neuroblastoma only two DLG2 isoforms were expressed: isoform 2 and isoform 7/8. Using the array data we could determine that higher expression of DLG members that contain L27 domains correlated to better survival and prognosis. Whilst DLG1 showed a decrease in both isoforms with increased INSS stage, only the full length L27 containing DLG2 transcripts DLG2-isoform 7/8 showed a decrease in expression in high stage neuroblastoma. We could show that the protein encoded by DLG2-isoform 7 could bind to LIN7A, and increased DLG2-isoform 7 gene expression increased the expression of LIN7A, this reduced neuroblastoma cell proliferation and viability, with increased BAX/BCL2 ratio indicating increased apoptosis.
conclusionWe have provided evidence that gene expression of the L27 domain containing DLG2-isoform 7/8 but not L27 domain lacking DLG2-isoform 2 is disrupted in neuroblastoma, in particular in the aggressive subsets of tumors. The presence of the complete L27 domain allows for the binding to LIN7A, which will control cell polarity and signaling, thus affecting cancer cell viability.
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