| Expression pattern: |
UP |
| Associated gene: |
CCND1 mRNA, ELAVL1/HuR |
| Associated microRNA: |
- |
| Biological function: |
promotes ER-positive breast cancer cell growth and G1/S cell cycle progression; promotes tumor growth; promotes endocrine therapy resistance and tamoxifen resistance |
| Molecular mechanism: |
Direct RNA-RNA pairing between circFOXK2 and CCND1 3′ UTR recruits ELAVL1/HuR to stabilize CCND1 mRNA and increase CCND1 protein, activating the CCND1-CDK4/6-p-RB-E2F axis |
| Biological pathway or process: |
cell cycle (promotes); proliferation (promotes); drug resistance (promotes); mRNA stability (promotes) |
| Detected method: |
Q
S
|
| Validation methods: |
circRNA-seq; RNA-seq; RT-qPCR; Back-Splice Junction PCR / divergent primers PCR; Sanger Sequencing; RNase R Treatment; Actinomycin D / DRB Stability Assay; Nuclear-Cytoplasmic Fractionation; FISH / smFISH; RIP (RNA Immunoprecipitation); RNA Pull-Down; Transfection; CCK8; Cell Cycle Assay; In Vivo Animal Model; IHC (Immunohistochemistry); Western Blot; Bioinformatics Analysis; Clinical Sample Validation |
| Clinical significance: |
circFOXK2 is significantly upregulated in clinical breast tumors and positively correlated with CCND1 in patient tumor tissues |
| Description: |
circFOXK2 is up-regulated in breast tumors and promotes ER-positive breast cancer growth and endocrine (tamoxifen) resistance. It directly pairs with the CCND1 3′ UTR and recruits ELAVL1/HuR to increase CCND1 mRNA stability, enhancing CCND1 protein and downstream RB phosphorylation/E2F-driven G1/S progression. ASO-mediated targeting of circFOXK2 suppresses xenograft tumor growth and restores tamoxifen sensitivity in resistant cells. |
| Confidence score: |
0.872 |