English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

NF-κB signaling is a hallmark of PFA1 ependymoma. Loss of LDOC1, through epigenetic silencing, leads to constitutively active NF-κB signaling and chronic IL-6 secretion. In this study, we investigate the loss of LDOC1 within the PFA tumor clusters. Using our PFA scRNAseq database, in which there are 5 clusters within the tumor cell compartment: mesenchymal (MEC), ciliated (CEC), transportive (TEC), and undifferentiated (UEC). LDOC1 expression was significantly reduced and had an inverse correlation with genes defining the unfavorable MEC subpopulation, predominate in PFA1. This is consistent with our findings that MEC was defined by an NF-κB2 signaling profile. In contrast, LDOC1 expression was higher and positively correlated with genes defining the favorable CEC subpopulation, mostly seen in PFA2. RELA expression, which we studied as a target of LDOC1, was not localized to MEC and was wide-spread throughout the PFA compartment. RELB, part of non-conical NF-κB signaling, was expressed only the MEC subpopulation correlating with IL-6 gene expression found only in this subpopulation. In MAF-811, a PFA cell line with more CEC-like gene phenotype, RELB co-immunoprecipates with the active form of NF-κB2 in both the nucleus and cytoplasm. IL-6 gene expression is almost completely lost when NF-κB2 is knock-down using shRNA. Additionally, loss of LDOC1 leads to over 3 fold increase in NF-κB2 expression. Combined with our previous work, this would suggest that NF-κB2 drives IL-6 expression by binding with RELB in MEC subpopulation and targeting loss of LDOC1 may shift the MEC subpopulation toward the more favorable CEC subpopulation.

EPEN-26. NON-CANONICAL NF-κB SIGNALING DRIVES MESENCHYMAL EPENDYMAL CELL SUBPOPULATION IN PFA EPENDYMOMA