| Expression pattern: |
DN |
| Associated gene: |
MSH2, MSH6, ATM, MutSalpha, p73 |
| Associated microRNA: |
- |
| Biological function: |
Promotes apoptosis; increases sensitivity to cisplatin (CDDP); attenuates chemoresistance; suppresses tumor growth in vivo |
| Molecular mechanism: |
circLIFR binds MSH2 in the nucleus, enhances MutSalpha-ATM interaction, increases ATM phosphorylation, stabilizes/upregulates p73, leading to apoptosis and enhanced cisplatin sensitivity |
| Biological pathway or process: |
apoptosis (promotes); drug resistance (inhibits); other pathway/process (promotes) |
| Detected method: |
Q
S
|
| Validation methods: |
RNA-seq; RT-qPCR; Clinical Sample Validation; Back-Splice Junction PCR / divergent primers PCR; RNase R Treatment; Sanger Sequencing; Actinomycin D / DRB Stability Assay; Nuclear-Cytoplasmic Fractionation; FISH / smFISH; RNA Pull-Down; RIP (RNA Immunoprecipitation); Co-IP; Western Blot; Transfection; CCK8; Annexin V/PI Flow Cytometry; In Vivo Animal Model; IHC (Immunohistochemistry); TUNEL; Survival Analysis; Bioinformatics Analysis |
| Clinical significance: |
CircLIFR expression was positively correlated with favorable prognosis; circLIFR and MSH2 status might be used as a stratification biomarker to select bladder cancer patients who may respond and benefit from CDDP treatment. |
| Description: |
CircLIFR (hsa_circ_0072309), derived from LIFR, is down-regulated in bladder cancer and higher expression is associated with better overall survival. It localizes mainly in the nucleus and binds MSH2, enhancing MutSalpha-ATM interaction and ATM phosphorylation to increase p73-mediated apoptosis, thereby sensitizing bladder cancer cells and xenografts/PDX tumors to cisplatin and reducing chemoresistance. |
| Confidence score: |
0.8931 |