| Expression pattern: |
UP |
| Associated gene: |
CELF1, hnRNPF, Sirt1, EIF2S1, GLIS3, Glis3-348aa, Ins2, Ngn3, Ccnd2 |
| Associated microRNA: |
- |
| Biological function: |
promotes beta-cell dysfunction, decreases insulin secretion, inhibits proliferation, promotes apoptosis, impairs glucose tolerance in vivo |
| Molecular mechanism: |
circGlis3 binds hnRNPF and blocks its nuclear translocation to reduce Sirt1/SIRT1; circGlis3 encodes Glis3-348aa that interacts with GLIS3 and inhibits its transcriptional activity; CELF1 promotes circGlis3 biogenesis |
| Biological pathway or process: |
proliferation (inhibits); apoptosis (promotes); ceRNA regulation (other) |
| Detected method: |
Q
|
| Validation methods: |
RT-qPCR; FISH / smFISH; RIP (RNA Immunoprecipitation); RNA Pull-Down; Transfection; Western Blot; Luciferase Reporter Assay; Co-IP; CCK8; EdU Staining; TUNEL; Annexin V/PI Flow Cytometry; ELISA; IF (Immunofluorescence); IHC (Immunohistochemistry); In Vivo Animal Model; Bioinformatics Analysis |
| Clinical significance: |
circGlis3 may be a potential therapeutic target for T2DM |
| Description: |
circGlis3 is upregulated in diabetic/lipotoxic beta cells and promotes beta-cell dysfunction in vitro and in vivo. Mechanistically, it (1) binds hnRNPF to block hnRNPF nuclear translocation and reduce Sirt1/SIRT1, and (2) encodes Glis3-348aa, which binds GLIS3 and suppresses GLIS3 transcriptional activity, reducing Ins2/Ngn3/Ccnd2 expression. |
| Confidence score: |
0.7616 |