| Expression pattern: |
UP |
| Associated gene: |
NSUN2, ALYREF, HSPA8, PINK1, Parkin |
| Associated microRNA: |
- |
| Biological function: |
promotes proliferation, cell viability, cell cycle progression and migration; inhibits apoptosis; induces mitophagy; promotes lung cancer progression in vitro and in vivo |
| Molecular mechanism: |
m5C modification by NSUN2 enables ALYREF-mediated nuclear export; circRREB1 binds HSPA8 and stabilizes it by inhibiting ubiquitin-dependent degradation, activating HSPA8/PINK1/Parkin signaling to induce mitophagy |
| Biological pathway or process: |
mitochondrial function (promotes); mitophagy (promotes); autophagy (promotes); apoptosis (inhibits); proliferation (promotes); cell cycle (promotes); migration (promotes); ceRNA regulation (other); ubiquitination (inhibits) |
| Detected method: |
Q
S
M
|
| Validation methods: |
RNA-seq; Microarray; RT-qPCR; Back-Splice Junction PCR / divergent primers PCR; RNase R Treatment; Sanger Sequencing; Actinomycin D / DRB Stability Assay; FISH / smFISH; Nuclear-Cytoplasmic Fractionation; Clinical Sample Validation; MeRIP / MeRIP-seq; CLIP; RIP (RNA Immunoprecipitation); RNA Pull-Down; Co-IP; Transfection; CCK8; EdU Staining; Cell Cycle Assay; Annexin V/PI Flow Cytometry; Transwell Assay; Wound Healing Assay; Western Blot; IHC (Immunohistochemistry); In Vivo Animal Model; Survival Analysis; ROC Analysis; Bioinformatics Analysis |
| Clinical significance: |
high circRREB1 expression is associated with poorer prognosis; potential diagnostic marker (AUC=0.859) |
| Description: |
circRREB1 is up-regulated in lung cancer and predicts poor prognosis. NSUN2-mediated m5C modification enables ALYREF-dependent nuclear export, and cytoplasmic circRREB1 binds/stabilizes HSPA8 by inhibiting its ubiquitination, activating the HSPA8-PINK1/Parkin axis to induce mitophagy and promote tumor progression. |
| Confidence score: |
0.904 |