| Expression pattern: |
UP |
| Associated gene: |
hnRNPA2B1, p53 pre-mRNA, HIF1alpha |
| Associated microRNA: |
- |
| Biological function: |
Promotes colorectal cancer cell proliferation and cell cycle progression, enhances serine/glycine metabolism and redox homeostasis, reduces ROS, and promotes tumor growth/tumorigenesis in a p53-dependent manner. |
| Molecular mechanism: |
CircMYH9 (nuclear, intron-derived) recruits/engages hnRNPA2B1 to prevent hnRNPA2B1 binding to m6A sites on the p53 3'UTR, thereby destabilizing p53 pre-mRNA and suppressing p53; reduced p53 relieves repression of PHGDH to promote serine/glycine metabolism and redox homeostasis. Under amino-acid deprivation, ROS induces HIF1alpha, which binds the MYH9 promoter to increase circMYH9 expression. |
| Biological pathway or process: |
proliferation (promotes); cell cycle (promotes); oxidative phosphorylation (other); ceRNA regulation (other); other pathway/process (promotes); m6A modification (other) |
| Detected method: |
Q
H
M
|
| Validation methods: |
Microarray; RT-qPCR; FISH / smFISH; Back-Splice Junction PCR / divergent primers PCR; RNase R Treatment; Sanger Sequencing; Nuclear-Cytoplasmic Fractionation; Clinical Sample Validation; Cohort Study; Survival Analysis; Transfection; CCK8; Colony Formation Assay; Cell Cycle Assay; In Vivo Animal Model; IHC (Immunohistochemistry); RNA-seq; RIP (RNA Immunoprecipitation); RNA Pull-Down; Luciferase Reporter Assay; ChIP / ChIP-seq; MeRIP / MeRIP-seq; Western Blot; Actinomycin D / DRB Stability Assay; IF (Immunofluorescence); Flow Cytometry（Non-apoptosis/cycle）; Bioinformatics Analysis |
| Clinical significance: |
High circMYH9 expression is associated with worse clinicopathological features and predicts shorter relapse-free survival and overall survival in CRC patients. |
| Description: |
circMYH9 (hsa_circ_0092283), an intron-derived circRNA from MYH9, is up-regulated in colorectal cancer and mainly localized in the nucleus. It promotes CRC growth by reducing p53 via hnRNPA2B1-associated destabilization of p53 pre-mRNA, which increases PHGDH-driven serine/glycine metabolism and supports redox homeostasis (lower ROS, higher NAD+/NADH and GSH recycling). High circMYH9 levels predict worse RFS/OS in CRC patients, and it enhances tumorigenesis in vivo including AOM/DSS models and xenografts. |
| Confidence score: |
0.904 |