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

ABSTRACT: 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. However, the role of circular RNAs (circRNAs) in TGF-β signaling remains largely unexplored. Here, we identify circTBRII(3-6), a circRNA derived from TGF-β type II receptor (TBRII) pre-mRNA, as a critical enhancer of TGF-β/SMAD signaling in breast cancer cells. Depletion of circTBRII(3-6) inhibits TGF-β-induced EMT, migration, and in vivo extravasation of breast cancer cells. Mechanistically, circTBRII(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 type I receptor (TBRI) mRNA in an N6-methyladenosine (m6A)-dependent manner, and thereby stabilizes TBRI and promotes its expression. Furthermore, IGF2BP3 knockdown reduces circTBRII(3-6)-mediated enhancement of TGF-β/SMAD signaling, as well as TGF-β-induced EMT and migration. Our findings identify circTBRII(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 circTBRII(3-6)-driven breast cancer cell plasticity.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Rayman Tjokrodirijo  

LAB HEAD: Peter A. van Veelen

PROVIDER: PXD061218 | Pride | 2026-04-27

REPOSITORIES: Pride