| Expression pattern: |
UP |
| Associated gene: |
Ago2, SIRT1, HIF-1alpha, RNA polymerase II, GLUT1, LDHA, HK2, PKM2 |
| Associated microRNA: |
miR-23b-3p |
| Biological function: |
Promotes gemcitabine chemoresistance of pancreatic cancer cells, enhances glycolysis, contributes to proliferation, and transmits hypoxia-associated drug resistance signals through exosomes. |
| Molecular mechanism: |
Hypoxia-induced exosomal circZNF91 acts as a miR-23b-3p sponge to upregulate SIRT1, stabilizes HIF-1alpha protein through SIRT1-dependent deacetylation, enhances HIF-1alpha-regulated glycolysis, and forms a positive feedback loop because HIF-1alpha transcriptionally upregulates circZNF91. |
| Biological pathway or process: |
HIF-1 signaling (promotes); glycolysis (promotes); chemoresistance (promotes); drug resistance (promotes); proliferation (promotes); ceRNA regulation (other) |
| Detected method: |
Q
M
|
| Validation methods: |
Back-Splice Junction PCR / divergent primers PCR; RNase R Treatment; Actinomycin D / DRB Stability Assay; RT-qPCR; Microarray; FISH / smFISH; Clinical Sample Validation; RIP (RNA Immunoprecipitation); RNA Pull-Down; Co-IP; ChIP / ChIP-seq; Luciferase Reporter Assay; Transfection; MTT; IHC (Immunohistochemistry); IF (Immunofluorescence); Western Blot; In Vivo Animal Model; Survival Analysis; Bioinformatics Analysis |
| Clinical significance: |
circZNF91 is overexpressed in pancreatic cancer tissues, correlates with glycolytic enzyme overexpression, and high circZNF91 expression is associated with shorter overall survival. |
| Description: |
In pancreatic cancer, hypoxia increases circZNF91 loading into exosomes, which transmit chemoresistance to normoxic cancer cells. circZNF91 sponges miR-23b-3p to release SIRT1, stabilizing HIF-1alpha through deacetylation and enhancing glycolysis-driven gemcitabine resistance. Clinically, circZNF91 is upregulated in PC tissues and high expression predicts shorter overall survival. |
| Confidence score: |
0.8921 |