| Expression pattern: |
UP |
| Associated gene: |
FUS, YWHAH, YAP, SOX9, hnRNPA2B1 |
| Associated microRNA: |
- |
| Biological function: |
Promotes RCC cell proliferation, invasion and migration; promotes tumor growth and metastasis by activating fibroblasts/CAFs via EV transfer and increasing IL-6 secretion. |
| Molecular mechanism: |
FUS promotes circEHD2 cyclization; circEHD2 binds YWHAH and is recruited with YAP to the SOX9 promoter to sustain SOX9 activation; hnRNPA2B1 mediates circEHD2 packaging into EVs which are taken up by fibroblasts to induce CAF activation and IL-6 secretion. |
| Biological pathway or process: |
proliferation (promotes); migration (promotes); invasion (promotes); metastasis (promotes); inflammation (promotes); other pathway/process (promotes) |
| Detected method: |
Q
H
S
M
|
| Validation methods: |
RNA-seq; Microarray; RT-qPCR; Back-Splice Junction PCR / divergent primers PCR; RNase R Treatment; Sanger Sequencing; Nuclear-Cytoplasmic Fractionation; FISH / smFISH; ISH (In Situ Hybridization); Clinical Sample Validation; ROC Analysis; Survival Analysis; Bioinformatics Analysis; RNA Pull-Down; RIP (RNA Immunoprecipitation); ChIRP; Luciferase Reporter Assay; Co-IP; ChIP / ChIP-seq; Transfection; CCK8; EdU Staining; Colony Formation Assay; Transwell Assay; In Vivo Animal Model; IHC (Immunohistochemistry); ELISA; Western Blot; H&E Staining |
| Clinical significance: |
circEHD2 is upregulated in ccRCC tissues and serum EVs (metastasis patients), can discriminate ccRCC from NAT by ROC analysis, and high tissue-circEHD2 is associated with poor PFS/OS and is an independent prognostic factor. |
| Description: |
circEHD2 (hsa_circ_0003146), derived from EHD2, is upregulated in ccRCC tissues and enriched in serum EVs from metastatic RCC patients, and high expression is associated with worse OS/PFS. Mechanistically, FUS promotes circEHD2 biogenesis; circEHD2 binds YWHAH and recruits YAP to the SOX9 promoter to sustain SOX9 activation, promoting RCC growth. hnRNPA2B1 mediates circEHD2 loading into EVs, enabling transfer to fibroblasts to induce CAF activation and IL-6 secretion, thereby promoting metastasis; targeting circEHD2 with ASO suppresses tumor growth in vivo. |
| Confidence score: |
0.9012 |