| Expression pattern: |
UP |
| Associated gene: |
CLK1, SRSF7, ATM, ATM-203, PD-L1 |
| Associated microRNA: |
- |
| Biological function: |
cALG8 promotes gemcitabine resistance, tumor cell proliferation, DNA damage repair, immunosuppression, and tumor growth in PDAC. |
| Molecular mechanism: |
cALG8 acts as a nuclear protein scaffold for the CLK1/SRSF7 complex, facilitates CLK1-mediated phosphorylation of SRSF7, promotes ATM-203 alternative splicing and ATM protein expression, enhances DNA damage repair through HR-related mechanisms, and contributes to PD-L1-associated immune suppression and gemcitabine resistance. |
| Biological pathway or process: |
chemoresistance (promotes); proliferation (promotes); immune regulation (other); other pathway/process (promotes) |
| Detected method: |
Q
H
S
|
| Validation methods: |
Back-Splice Junction PCR / divergent primers PCR; RNase R Treatment; Sanger Sequencing; Actinomycin D / DRB Stability Assay; RT-qPCR; circRNA-seq; RNA-seq; FISH / smFISH; ISH (In Situ Hybridization); IHC (Immunohistochemistry); IF (Immunofluorescence); Nuclear-Cytoplasmic Fractionation; Clinical Sample Validation; RIP (RNA Immunoprecipitation); RNA Pull-Down; Co-IP; Luciferase Reporter Assay; Transfection; CCK8; Flow Cytometry（Non-apoptosis/cycle）; In Vivo Animal Model; H&E Staining; ELISA; Western Blot; Cohort Study; Survival Analysis; Bioinformatics Analysis |
| Clinical significance: |
High cALG8 expression is associated with gemcitabine-resistant PDAC and poor prognosis; ASO targeting of cALG8 may sensitize tumors to gemcitabine and immunotherapy. |
| Description: |
This study identifies hsa_circ_0007767/cALG8 as a highly up-regulated circRNA in gemcitabine-resistant PDAC cells and patient tumors. Nuclear cALG8 functions as a scaffold for the CLK1/SRSF7 splicing complex, promoting SRSF7 phosphorylation, ATM-203 splicing, DNA damage repair, chemoresistance, and immune suppression; ASO-mediated cALG8 targeting reverses resistance and enhances anti-tumor immunity. |
| Confidence score: |
0.904 |