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Omics · study · 2026

circTGFBR2(3-6) acts as an assembly platform for IGF2BP3 protein and TGFBR1 mRNA to enhance breast cancer cell plasticity

Listed in NCBI GEO

Transforming growth factor (TGF)-β signaling is a key driver to induce epithelial-to-mesenchymal transition (EMT), a process that enhances cancer cell plasticity and metastatic potential.

Description

However, the role of circular RNAs (circRNAs) in TGF-β signaling remains largely unexplored. Here, we identify circTGFBR2(3-6), a circRNA derived from TGF-β receptor 2 (TGFBR2) pre-mRNA, as a critical enhancer of TGF-β/SMAD signaling in breast cancer cells.

Depletion of circTGFBR2(3-6) inhibits TGF-β-induced EMT, migration, and in vivo extravasation of breast cancer cells. Mechanistically, circTGFBR2(3-6) acts as a scaffold that facilitates the interaction between the RNA-binding protein insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3) and TGF-β receptor 1 (TGFBR1) mRNA in an N6-methyladenosine (m6A)-dependent manner, and thereby stabilizes TGFBR1 and promotes its expression.

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Furthermore, IGF2BP3 knockdown reduces circTGFBR2(3-6)-mediated enhancement of TGF-β/SMAD signaling and TGF-β-induced EMT and migration. Our findings identify circTGFBR2(3-6) as a novel enforcer of TGF-β/SMAD signaling at the receptor level and highlight IGF2BP3 as a critical m6A reader that mediates circTGFBR2(3-6)-driven breast cancer cell plasticity.

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From keywords
Life Sciences
Inferred from text
Cancer 75%
Provenance · 1 source records, 8 field assertions
SourceKeyLast seenRaw
NCBI GEOGSE30313212 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: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