| Expression pattern: |
UP |
| Associated gene: |
ERbeta, VE-cadherin |
| Associated microRNA: |
miR-125a-5p, miR-125b-5p |
| Biological function: |
Promotes vasculogenic mimicry formation and metastasis in RCC and contributes to TKI (sunitinib/axitinib)-induced VM by increasing VE-cadherin via miR-125-5p sponging; circDGKD knockdown suppresses VM and metastasis and improves survival in an orthotopic model. |
| Molecular mechanism: |
ERbeta transcriptionally up-regulates circDGKD (from DGKD), and circDGKD acts as a miRNA sponge for the miR-125-5p family, thereby relieving repression of VE-cadherin (CDH5) and promoting VM formation. |
| Biological pathway or process: |
ceRNA regulation (promotes); metastasis (promotes); invasion (other); migration (other) |
| Detected method: |
Q
|
| Validation methods: |
RT-qPCR; RNase R Treatment; RNA Pull-Down; Luciferase Reporter Assay; FISH / smFISH; Transfection; In Vivo Animal Model; Western Blot; Bioinformatics Analysis; ChIP / ChIP-seq; Clinical Sample Validation; IHC (Immunohistochemistry); Tube Formation Assay |
| Clinical significance: |
Targeting circDGKD may improve therapeutic efficacy of TKIs in metastatic RCC by suppressing TKI-induced vasculogenic mimicry and metastasis. |
| Description: |
In RCC, TKI-induced ERbeta transcriptionally elevates circDGKD (DGKD-derived). circDGKD sponges miR-125a-5p/miR-125b-5p to increase VE-cadherin (CDH5), thereby promoting vasculogenic mimicry and metastasis; circDGKD silencing blocks these effects and improves survival in an orthotopic model. |
| Confidence score: |
0.8294 |