| Expression pattern: |
UP |
| Associated gene: |
MSI2, ENO1 mRNA, ENO1, RPS3, TLR8, NF-kappaB |
| Associated microRNA: |
miR-515-5p |
| Biological function: |
Promotes ALL cell proliferation, colony formation, cell cycle progression, tumor growth, and survival; inhibits apoptosis. |
| Molecular mechanism: |
circNR3C1 directly binds MSI2 and prevents ubiquitination-mediated MSI2 degradation, thereby stabilizing MSI2 protein; stabilized MSI2 enhances ENO1 mRNA stability, increasing ENO1 expression, which enhances RPS3 protein stability. circNR3C1 also modulates NF-kappaB activation through the miR-515-5p/TLR8 axis. |
| Biological pathway or process: |
proliferation (promotes); apoptosis (inhibits); cell cycle (promotes); mRNA stability (promotes); ubiquitination (inhibits); NF-kappaB (promotes); inflammation (promotes); ceRNA regulation (promotes) |
| Detected method: |
Q
|
| Validation methods: |
Back-Splice Junction PCR / divergent primers PCR; RNase R Treatment; Sanger Sequencing; RT-qPCR; Actinomycin D / DRB Stability Assay; Nuclear-Cytoplasmic Fractionation; RIP (RNA Immunoprecipitation); RNA Pull-Down; Co-IP; Transfection; CCK8; Colony Formation Assay; Annexin V/PI Flow Cytometry; Cell Cycle Assay; In Vivo Animal Model; IHC (Immunohistochemistry); Western Blot; Bioinformatics Analysis |
| Clinical significance: |
The circNR3C1/MSI2/ENO1/RPS3 axis represents a potential therapeutic target for acute lymphoblastic leukemia. |
| Description: |
circNR3C1 is upregulated in B-ALL cell lines and acts as an oncogenic circRNA in ALL models. It promotes proliferation, cell cycle progression, tumor growth, and survival while inhibiting apoptosis by stabilizing MSI2 protein, enhancing ENO1 mRNA stability, and increasing ENO1/RPS3 expression; it also regulates inflammatory NF-kappaB signaling through a miR-515-5p/TLR8 axis. |
| Confidence score: |
0.8478 |