| Expression pattern: |
UP |
| Associated gene: |
ERalpha, QKI, RNF181 |
| Associated microRNA: |
- |
| Biological function: |
Promotes breast cancer cell proliferation and tumor growth; promotes tamoxifen resistance; enhances ERalpha signaling by stabilizing ERalpha protein. |
| Molecular mechanism: |
circRNA-SFMBT2 directly binds ERalpha (AF2 and DBD domains) and recruits RNF181 to ERalpha, differentially regulating K48- and K63-linked ubiquitination to enhance ERalpha stability and ERalpha target gene transcription; QKI promotes circRNA-SFMBT2 biogenesis. |
| Biological pathway or process: |
proliferation (promotes); cell cycle (promotes); apoptosis (inhibits); drug resistance (promotes); ubiquitination (other pathway/process); ERK (not specified) |
| Detected method: |
Q
|
| Validation methods: |
Bioinformatics Analysis; RNA-seq; RT-qPCR; Back-Splice Junction PCR / divergent primers PCR; Sanger Sequencing; Actinomycin D / DRB Stability Assay; RNase R Treatment; FISH / smFISH; Nuclear-Cytoplasmic Fractionation; RIP (RNA Immunoprecipitation); RNA Pull-Down; Luciferase Reporter Assay; Transfection; MTT; EdU Staining; Colony Formation Assay; Annexin V/PI Flow Cytometry; Cell Cycle Assay; Western Blot; IF (Immunofluorescence); In Vivo Animal Model; IHC (Immunohistochemistry); Clinical Sample Validation; Cohort Study; Survival Analysis |
| Clinical significance: |
High circRNA-SFMBT2 expression was associated with larger tumor size and poor prognosis in patients with ER+ breast cancer. |
| Description: |
circRNA-SFMBT2 is up-regulated in ER+ breast cancer and further induced by tamoxifen/estrogen deprivation, promoting proliferation and tamoxifen resistance. It binds ERalpha and acts as a scaffold to recruit RNF181, altering ERalpha ubiquitination (decreasing K48-linked while increasing K63-linked) to stabilize ERalpha and enhance ERalpha signaling and target-gene expression. |
| Confidence score: |
0.8981 |