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Text · study · 2026

RNA-binding protein CIRBP mediates PKM2 intron retention to negatively regulate multiple myeloma progression and macrophage alternative activation

Listed in NCBI GEO

Multiple myeloma (MM) is a systemic malignancy characterized by the induction of osteolytic lesions.

Description

Cold-inducible RNA binding protein (CIRBP) has garnered attention in cancer research due to its dual role as either an oncogene or a tumor suppressor. In this study, publicly available single-cell RNA sequencing data, MM cell lines, and an in vivo xenograft model are utilized to assess the biological significance of CIRBP in MM.

Analysis reveals frequent communication between MM cells and macrophages, alongside decreased CIRBP expression in patients. Functionally, CIRBP overexpression in MM cells inhibits short- and long-term viability, suppresses proliferation, and reduces tumor burden in vitro and in vivo. Furthermore, co-culture experiments confirm that CIRBP-expressing MM cells suppress macrophage chemotaxis and macrophage alternative activation, while CIRBP knockdown has opposite effects.

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Mechanistically, CIRBP binds to intron1 of pyruvate kinase M2 (PKM2) precursor messenger RNA (pre-mRNA), inhibiting its splicing and promoting its nonsense-mediated decay, ultimately leading to downregulation of PKM2. Elevated levels of PKM2 rescue the CIRBP-mediated suppression of macrophage chemotaxis and macrophage alternative activation. Our findings support the notion of CIRBP as a candidate tumor suppressor in MM and unveil a post-transcriptional regulatory mechanism governing PKM2-mediated macrophage plasticity.

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Stated by source
Homo sapiens · Other
From keywords
Life Sciences
Inferred from text
Cancer 75% · RNA sequencing 75% · Sequencing 75% · Single-cell RNA sequencing 75%
Provenance · 1 source records, 11 field assertions
SourceKeyLast seenRaw
NCBI GEOGSE33905814 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 (75%)
concepts[field].local:field:life-sciencesmapping · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[method].geo_series_type:othersource · NCBI GEOconnector:ncbi_geo@1.0.0/gdstype
concepts[modality].local:modality:rna-seqenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (75%)
concepts[modality].local:modality:sequencingenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (75%)
concepts[modality].local:modality:single-cell-rna-seqenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (75%)
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