| Expression pattern: |
UP |
| Associated gene: |
INSIG1, CUL5-ASB6 complex, ASB6, CUL5, EIF4A3 |
| Associated microRNA: |
- |
| Biological function: |
promotes CRC proliferation and metastasis; induces cholesterol biosynthesis by promoting INSIG1 degradation |
| Molecular mechanism: |
circINSIG1 encodes circINSIG1-121, which recruits the CUL5-ASB6 ubiquitin E3 ligase complex to promote K48-linked ubiquitination of INSIG1 (K156/K158), leading to ubiquitin-proteasome degradation of INSIG1 and activation of SREBP2-driven cholesterol biosynthesis |
| Biological pathway or process: |
cholesterol biosynthesis (promotes); proliferation (promotes); metastasis (promotes); ubiquitination (promotes); other pathway/process (promotes) |
| 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); Clinical Sample Validation; Survival Analysis; Transfection; Colony Formation Assay; Transwell Assay; In Vivo Animal Model; H&E Staining; IHC (Immunohistochemistry); Western Blot; RIP (RNA Immunoprecipitation); RNA Pull-Down; Co-IP; Luciferase Reporter Assay; Bioinformatics Analysis |
| Clinical significance: |
upregulated in CRC tissues and correlated with advanced clinical stages and poor survival |
| Description: |
circINSIG1 (hsa_circ_0133744) is upregulated in colorectal cancer and mainly localized in the cytoplasm. It encodes a 121-aa peptide (circINSIG1-121) that recruits the CUL5-ASB6 E3 ligase complex to enhance K48-linked ubiquitination and proteasomal degradation of INSIG1, thereby activating SREBP2-driven cholesterol biosynthesis and promoting CRC proliferation and metastasis; high circINSIG1 associates with advanced stage and poor survival. |
| Confidence score: |
0.8978 |