| Expression pattern: |
UP |
| Associated gene: |
CCNE2, USP10, p53, AGO2 |
| Associated microRNA: |
miR-1244 |
| Biological function: |
promotes CRC cell proliferation and tumor growth; increases cell cycle progression; sensitizes response to anlotinib (high circHAS2 marks higher sensitivity) |
| Molecular mechanism: |
ceRNA sponge of miR-1244 to activate CCNE2; binds USP10 to disrupt USP10-p53 interaction, promoting p53 nuclear export and ubiquitin-mediated degradation, reducing p21 and increasing CCNE2 |
| Biological pathway or process: |
proliferation (promotes); cell cycle (promotes); ceRNA regulation (promotes); p53 signaling (inhibits) |
| Detected method: |
Q
H
S
|
| Validation methods: |
RNA-seq; RT-qPCR; Back-Splice Junction PCR / divergent primers PCR; Sanger Sequencing; RNase R Treatment; Actinomycin D / DRB Stability Assay; Nuclear-Cytoplasmic Fractionation; FISH / smFISH; ISH (In Situ Hybridization); RIP (RNA Immunoprecipitation); RNA Pull-Down; Luciferase Reporter Assay; Transfection; CCK8; EdU Staining; Colony Formation Assay; Cell Cycle Assay; Western Blot; Co-IP; IHC (Immunohistochemistry); In Vivo Animal Model; Survival Analysis; ROC Analysis; Clinical Sample Validation; Cohort Study; Bioinformatics Analysis |
| Clinical significance: |
High circHAS2 expression correlates with poor prognosis in CRC and serves as a biomarker predictive of anlotinib sensitivity/response. |
| Description: |
CircHAS2 is up-regulated in colorectal cancer and promotes proliferation/cell-cycle progression by sponging miR-1244 to increase CCNE2 and by binding USP10 to disrupt USP10-p53, enhancing p53 nuclear export and degradation (decreasing p21 and further increasing CCNE2). It is downregulated by anlotinib and serves as a predictive biomarker of anlotinib sensitivity in PDO/PDX models and in a phase II cohort. |
| Confidence score: |
0.9043 |