| Expression pattern: |
DN |
| Associated gene: |
APC mRNA, ERBB3, EGFR |
| Associated microRNA: |
miR-6815-3p |
| Biological function: |
Inhibits gastric cancer cell proliferation, migration, invasion, and peritoneal metastasis; sensitizes gastric cancer cells to gefitinib and helps overcome gefitinib resistance. |
| Molecular mechanism: |
Acts as a ceRNA sponging miR-6815-3p to relieve repression of APC mRNA and inactivate Wnt/beta-catenin signaling; undergoes rolling translation to produce circZFAND6-aa peptide that binds ERBB3, hindering EGFR tyrosine kinase activity and downstream AKT signaling to overcome gefitinib resistance. |
| Biological pathway or process: |
Wnt/beta-catenin (inhibits); PI3K/AKT (inhibits); proliferation (inhibits); migration (inhibits); invasion (inhibits); metastasis (inhibits); EMT (inhibits); drug resistance (inhibits); ceRNA regulation (promotes) |
| Detected method: |
Q
S
M
|
| Validation methods: |
RNA-seq; Microarray; RT-qPCR; Back-Splice Junction PCR / divergent primers PCR; RNase R Treatment; Sanger Sequencing; FISH / smFISH; RIP (RNA Immunoprecipitation); Luciferase Reporter Assay; Transfection; CCK8; Colony Formation Assay; Transwell Assay; Western Blot; In Vivo Animal Model; IHC (Immunohistochemistry); Survival Analysis; Bioinformatics Analysis; Co-IP |
| Clinical significance: |
Reduced circZFAND6 expression is independently linked to poor prognosis in GC patients; downregulation predicts poor prognosis and circZFAND6 could be a prognostic biomarker. |
| Description: |
circZFAND6 is down-regulated in gastric cancer and peritoneal dissemination and functions as a tumor suppressor. It sponges miR-6815-3p to upregulate APC and inactivate Wnt/beta-catenin signaling, inhibiting proliferation and metastasis/EMT. In addition, circZFAND6 undergoes rolling translation to produce circZFAND6-aa that binds ERBB3 and dampens EGFR-driven PI3K/AKT signaling, improving gefitinib sensitivity and reducing gefitinib resistance. |
| Confidence score: |
0.8769 |