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Omics · study · 2026

Differentially expressed genes upon the overexpression of MENIN in QGP1 cells

Listed in NCBI GEO

Pancreatic neuroendocrine tumours (PNETs) are graded based on their proliferation rate marked by Ki-67, where increased proliferation is associated with poorer prognosis.

Description

However, detailed molecular mechanisms underlying their proliferation remain to be clarified. In this study, we have identified NF-κB signalling as a novel pathway that is hyperactivated in PNETs via single cell analyses and immunofluorescence staining of human PNET tissues.

Furthermore, we have confirmed that the NF-κB subunit RelA/p65 is implicated in PNET proliferation in vitro and in vivo and demonstrated that depleting or inhibiting RelA/p65 significantly reduces the proliferation rate of QGP-1 cells. Separately, we have uncovered that menin (encoded by the MEN1 gene), a tumour suppressor commonly mutated in PNETs, represses PNET proliferation in a RelA/p65-dependent manner, by downregulating the expression of RelA/p65 target genes associated with proliferation.

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We have identified the NR4A1 gene as one such target and confirmed that its expression is highly upregulated in MEN1 mutated PNETs. Additionally, the depletion or chemical inhibition of NR4A1 significantly reduced cellular proliferation. Therefore, serving as a proof of concept that RelA/p65 target genes such as NR4A1 is implicated in PNET proliferation and can be targeted for therapeutic treatment.

Overall, our study has identified the NF-κB signalling pathway and a subset of its genes such as NR4A1 to be responsible for PNET proliferation, opening new potential therapeutic options for both PNETs and MEN1-mutated PNETs.

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Life Sciences
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Cancer 65%
Provenance · 1 source records, 8 field assertions
SourceKeyLast seenRaw
NCBI GEOGSE24254913 d agoJSON v1
FieldAssertionExtractorEvidence
access_levelsource · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[disease].local:disease:cancerenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (65%)
concepts[field].local:field:life-sciencesmapping · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencingsource · NCBI GEOconnector:ncbi_geo@1.0.0/gdstype
concepts[organism].NCBITaxon:9606source · NCBI GEOconnector:ncbi_geo@1.0.0/taxon
descriptionsource · NCBI GEOconnector:ncbi_geo@1.0.0/summary
publication_datesource · NCBI GEOconnector:ncbi_geo@1.0.0
titlesource · NCBI GEOconnector:ncbi_geo@1.0.0/title