| Expression pattern: |
UP |
| Associated gene: |
ILF3, IL36gamma, exportin-5 |
| Associated microRNA: |
- |
| Biological function: |
promotes tumor growth and immune evasion by reducing NK cell infiltration and impairing NK cells' granzyme B and IFN-gamma production; promotes anti-PD-1 resistance |
| Molecular mechanism: |
circPHLPP2 binds ILF3, promotes nuclear accumulation of ILF3, and enhances IL36gamma transcription; circPHLPP2 inhibits exportin-5 binding to ILF3 |
| Biological pathway or process: |
immune regulation (inhibits); proliferation (promotes); ceRNA regulation (other) |
| Detected method: |
Q
M
|
| Validation methods: |
Microarray; RNase R Treatment; RT-qPCR; Back-Splice Junction PCR / divergent primers PCR; Sanger Sequencing; Actinomycin D / DRB Stability Assay; FISH / smFISH; Nuclear-Cytoplasmic Fractionation; Clinical Sample Validation; Transfection; MTT; Colony Formation Assay; In Vivo Animal Model; Flow Cytometry（Non-apoptosis/cycle）; RIP (RNA Immunoprecipitation); RNA Pull-Down; Co-IP; Luciferase Reporter Assay; Western Blot; RNA-seq; IHC (Immunohistochemistry); Survival Analysis; Bioinformatics Analysis |
| Clinical significance: |
high expression of circPHLPP2 is associated with anti-PD-1 resistance and shorter overall survival in CRC patients |
| Description: |
circPHLPP2 (hsa_circ_0003681, from PHLPP2) is up-regulated in CRC, especially in anti-PD-1-resistant MSS/pMMR patients, and high expression predicts worse overall survival. Functionally, it promotes tumor growth in vivo and anti-PD-1 resistance by binding ILF3 to drive nuclear ILF3 accumulation and increase IL36gamma transcription, leading to reduced NK-cell infiltration and reduced granzyme B/IFN-gamma production. |
| Confidence score: |
0.8978 |