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.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE339nnn/GSE339058 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE339058 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1496888 ncbi.nlm.nih.gov/bioproject/PRJNA1496888 ↗
project · from NCBI GEO
Topics
- 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
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE339058 | 14 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[disease].local:disease:cancer | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[method].geo_series_type:other | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[modality].local:modality:rna-seq | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[modality].local:modality:sequencing | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[modality].local:modality:single-cell-rna-seq | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[organism].NCBITaxon:9606 | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /taxon |
| description | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /summary |
| publication_date | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| title | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /title |