| Expression pattern: |
UP |
| Associated gene: |
TOP2A |
| Associated microRNA: |
miR-345-5p, miR-93-3p |
| Biological function: |
promotes sorafenib resistance, promotes proliferation, and suppresses apoptosis in HCC cells |
| Molecular mechanism: |
cDCBLD2 acts as a ceRNA/miRNA sponge for miR-345-5p, stabilizing TOP2A mRNA and increasing TOP2A expression, thereby inhibiting caspase-3-mediated apoptosis and reducing sorafenib cytotoxicity |
| Biological pathway or process: |
chemoresistance (promotes); apoptosis (inhibits); proliferation (promotes); ceRNA regulation (promotes); mRNA stability (promotes) |
| Detected method: |
Q
M
|
| Validation methods: |
Microarray; RT-qPCR; Back-Splice Junction PCR / divergent primers PCR; RNase R Treatment; Actinomycin D / DRB Stability Assay; FISH / smFISH; Nuclear-Cytoplasmic Fractionation; RNA Pull-Down; Luciferase Reporter Assay; Transfection; CCK8; Annexin V/PI Flow Cytometry; Western Blot; In Vivo Animal Model |
| Clinical significance: |
siRNA-mediated targeting of cDCBLD2 increased sensitivity to sorafenib in a PDX model, suggesting clinical potential for sorafenib-resistant HCC patients |
| Description: |
cDCBLD2 (circRNA_103420 / hsa_circ_0066631) is upregulated in sorafenib-resistant HCC cells and promotes resistance by enhancing proliferation and inhibiting apoptosis. Mechanistically, it sponges miR-345-5p to stabilize TOP2A mRNA (via CDS-binding miRNA regulation), increasing TOP2A and dampening caspase-3-mediated apoptosis; cDCBLD2 knockdown sensitizes tumors to sorafenib in a PDX model. |
| Confidence score: |
0.7796 |