| Expression pattern: |
UP |
| Associated gene: |
SLX4, IPO13, UBC9, CXCL10, PD-L1 |
| Associated microRNA: |
- |
| Biological function: |
Promotes chemotherapy-induced senescence, increases chemosensitivity, promotes CD8+ T-cell infiltration via SASP (CXCL10), but induces immune escape by upregulating PD-L1. |
| Molecular mechanism: |
cCCT2 competitively binds IPO13, blocks UBC9 nuclear import, reduces SLX4 SUMOylation, increases SLX4 export and ubiquitin-proteasome degradation, inhibits SLX4 condensate-mediated DNA damage repair, leading to DNA damage accumulation and senescence; SASP CXCL10 recruits CD8+ T-cells; PD-L1 upregulation causes exhaustion and is reversible by anti-PD-L1. |
| Biological pathway or process: |
m6A modification (not specified) |
| Detected method: |
Q
H
S
|
| Validation methods: |
circRNA-seq; RT-qPCR; ISH (In Situ Hybridization); Back-Splice Junction PCR / divergent primers PCR; RNase R Treatment; Sanger Sequencing; Actinomycin D / DRB Stability Assay; FISH / smFISH; Nuclear-Cytoplasmic Fractionation; Clinical Sample Validation; Transfection; CCK8; EdU Staining; Annexin V/PI Flow Cytometry; Western Blot; RNA Pull-Down; RIP (RNA Immunoprecipitation); CLIP; IF (Immunofluorescence); Luciferase Reporter Assay; Transwell Assay; ELISA; In Vivo Animal Model; IHC (Immunohistochemistry); H&E Staining; Survival Analysis; Bioinformatics Analysis |
| Clinical significance: |
High cCCT2 expression was associated with better prognosis; cCCT2 was upregulated in chemotherapy-responsive PDAC tissues and PDOs and suggested as a predictive biomarker for PDAC treatment. |
| Description: |
In PDAC, cCCT2 (hsa_circ_0002940) is upregulated in chemotherapy-responsive cases and promotes FOLFIRINOX-induced senescence and chemosensitivity by impairing SLX4-dependent DNA damage repair via IPO13/UBC9-regulated SUMOylation. Senescent tumor cells secrete CXCL10 to recruit CD8+ T-cells but also upregulate PD-L1, enabling immune escape; sequential anti-PD-L1 therapy restores cytotoxic function. SenExo-cCCT2 is an exosome-based delivery strategy to exploit these effects therapeutically. |
| Confidence score: |
0.8988 |