| Expression pattern: |
UP |
| Associated gene: |
MST1, MST2, LATS1/2, YAP, TAZ |
| Associated microRNA: |
- |
| Biological function: |
promotes cisplatin resistance; suppresses apoptosis under cisplatin treatment; promotes colony formation under cisplatin treatment |
| Molecular mechanism: |
circ_ARHGEF28 directly binds MST1/2 SARAH coiled-coil domains to inhibit MST1/2 dimerization, suppress Hippo pathway activation, reduce YAP/TAZ ubiquitination and degradation, and increase YAP/TAZ accumulation and nuclear translocation |
| Biological pathway or process: |
Hippo/YAP (inhibits); drug resistance (promotes); apoptosis (inhibits); proliferation (promotes) |
| Detected method: |
Q
H
S
|
| Validation methods: |
RNA-seq; RT-qPCR; RNase R Treatment; Actinomycin D / DRB Stability Assay; divergent primers PCR; FISH / smFISH; Nuclear-Cytoplasmic Fractionation; ISH (In Situ Hybridization); Clinical Sample Validation; Transfection; Colony Formation Assay; Annexin V/PI Flow Cytometry; In Vivo Animal Model; RNA Pull-Down; RIP (RNA Immunoprecipitation); Co-IP; Western Blot; IF (Immunofluorescence); Survival Analysis; Bioinformatics Analysis |
| Clinical significance: |
High expression of circ_ARHGEF28 correlated with significantly worse progression-free survival (PFS) in patients treated with cisplatin-based chemotherapy and was an independent prognostic factor for PFS |
| Description: |
circ_ARHGEF28 is up-regulated in cisplatin-resistant ovarian cancer tissues/cells and promotes cisplatin resistance. Mechanistically, it binds MST1/2 (SARAH domains) to inhibit MST1/2 dimerization, suppressing Hippo signaling and favoring YAP/TAZ accumulation and nuclear translocation; clinically, high circ_ARHGEF28 is associated with worse PFS. |
| Confidence score: |
0.8778 |