| Expression pattern: |
DN |
| Associated gene: |
RNF125, JAK1, STAT3, AGO2 |
| Associated microRNA: |
miR-16-5p |
| Biological function: |
CircPTTG1IP acts as a tumor suppressor in HCC; its elevation inhibits HCC cell viability, proliferation, migration, invasion, tumor growth and metastasis, while promoting apoptosis. Low circPTTG1IP promotes HCC progression and contributes to tumor-associated macrophage recruitment and M2 polarization through the JAK1 axis. |
| Molecular mechanism: |
CircPTTG1IP functions as a cytoplasmic ceRNA that sponges miR-16-5p, thereby increasing RNF125 expression; RNF125 ubiquitinates and degrades JAK1 protein, inhibiting the JAK1-STAT3 pathway. Low circPTTG1IP activates the JAK1 axis, and filgotinib suppresses the malignant phenotype and TAM activation triggered by circPTTG1IP loss. |
| Biological pathway or process: |
JAK/STAT (inhibits); proliferation (inhibits); migration (inhibits); invasion (inhibits); metastasis (inhibits); apoptosis (promotes); ceRNA regulation (other); ubiquitination (promotes); immune regulation (inhibits); macrophage polarization (inhibits); inflammation (inhibits); other pathway/process (other) |
| Detected method: |
Q
S
|
| Validation methods: |
Back-Splice Junction PCR / divergent primers PCR; RNase R Treatment; Sanger Sequencing; circRNA-seq; Actinomycin D / DRB Stability Assay; RT-qPCR; FISH / smFISH; IHC (Immunohistochemistry); IF (Immunofluorescence); Clinical Sample Validation; RIP (RNA Immunoprecipitation); circRIP; RNA Pull-Down; Co-IP; Luciferase Reporter Assay; Transfection; CCK8; Colony Formation Assay; Annexin V/PI Flow Cytometry; Flow Cytometry（Non-apoptosis/cycle）; Transwell Assay; Wound Healing Assay; In Vivo Animal Model; H&E Staining; ELISA; Western Blot; Cohort Study; Survival Analysis; Bioinformatics Analysis |
| Clinical significance: |
Low circPTTG1IP expression is associated with poor prognosis in HCC patients; circPTTG1IP could serve as a biomarker for predicting prognosis and as a novel therapeutic target for HCC. Patients with low circPTTG1IP may benefit from filgotinib treatment. |
| Description: |
circPTTG1IP is a human chromosome 21-derived tumor suppressor circRNA that is downregulated in HCC and whose low expression predicts poor prognosis. It suppresses HCC malignancy by sponging miR-16-5p to increase RNF125, leading to ubiquitination and degradation of JAK1 and inhibition of JAK1-STAT3 signaling. Loss of circPTTG1IP promotes tumor progression and macrophage recruitment/M2 polarization, while the JAK1 inhibitor filgotinib counteracts these effects. |
| Confidence score: |
0.8984 |