| Expression pattern: |
DN |
| Associated gene: |
IGF2BP2, c-myc mRNA, c-MYC |
| Associated microRNA: |
- |
| Biological function: |
sensitizes BETi-resistant TNBC to BET inhibitors; inhibits c-MYC translation; represses acquired BETi resistance; enhances BETi therapeutic response and tumor regression when combined with OTX015 |
| Molecular mechanism: |
BISC binds IGF2BP2 and competitively inhibits recruitment of c-myc mRNA to IGF2BP2, thereby suppressing IGF2BP2-mediated c-MYC translation; interaction depends on “CAC-|9-12|-XGGX” motifs |
| Biological pathway or process: |
drug resistance (inhibits); proliferation (inhibits); apoptosis (other) |
| Detected method: |
Q
|
| Validation methods: |
RIP (RNA Immunoprecipitation); RNA-seq; RT-qPCR; RNase R Treatment; Back-Splice Junction PCR / divergent primers PCR; Sanger Sequencing; FISH / smFISH; Nuclear-Cytoplasmic Fractionation; RNA Pull-Down; Western Blot; Luciferase Reporter Assay; Transfection; CCK8; Colony Formation Assay; In Vivo Animal Model; Bioinformatics Analysis |
| Clinical significance: |
- |
| Description: |
BISC (hsa_circ_0001573), derived from RREB1, is down-regulated in BETi-resistant TNBC cells. It directly binds the RBP IGF2BP2 (via “CAC-|9-12|-XGGX” motifs) and antagonizes IGF2BP2 recruitment to c-myc mRNA, suppressing c-MYC translation and restoring sensitivity to BET inhibitors; in vivo delivery of circularized BISC plus OTX015 causes tumor regression in resistant xenografts. |
| Confidence score: |
0.8118 |