| Expression pattern: |
UP |
| Associated gene: |
FOXP1, SRSF4, U2AF1, Smad2, RNaseH1, S9.6 |
| Associated microRNA: |
- |
| Biological function: |
ca-circFOXP1 promotes hypoxia-induced mPASMC proliferation, cell cycle progression, migration, pulmonary vascular remodeling, and distal pulmonary vascular fibrosis; knockdown of ca-circFOXP1 attenuates SuHX-induced PH-related changes. |
| Molecular mechanism: |
SRSF4 upregulates ca-circFOXP1 by regulating splicing of FOXP1 pre-mRNA exons 6 and 9. m6A modification promotes R-loop formation between ca-circFOXP1 and the host gene FOXP1, reducing FOXP1 protein expression and increasing Smad2 phosphorylation to promote PASMC proliferation. |
| Biological pathway or process: |
proliferation (promotes); cell cycle (promotes); migration (promotes); fibrosis (promotes); TGF-beta/SMAD (promotes); m6A modification (other); other pathway/process (other) |
| Detected method: |
Q
H
M
|
| Validation methods: |
Back-Splice Junction PCR / divergent primers PCR; RNase R Treatment; Sanger Sequencing; RT-qPCR; FISH / smFISH; Nuclear-Cytoplasmic Fractionation; Clinical Sample Validation; RIP (RNA Immunoprecipitation); RNA Pull-Down; Co-IP; Transfection; CCK8; EdU Staining; Cell Cycle Assay; Wound Healing Assay; IF (Immunofluorescence); In Vivo Animal Model; H&E Staining; Western Blot; Bioinformatics Analysis |
| Clinical significance: |
ca-circFOXP1 is proposed as a potential diagnostic and therapeutic target for hypoxia-induced PH. |
| Description: |
ca-circFOXP1 is up-regulated in hypoxic PH models and hypoxic PASMCs. It promotes PASMC proliferation, cell cycle progression, migration, pulmonary vascular remodeling, and fibrosis by forming an m6A-dependent R loop with the FOXP1 host gene, reducing FOXP1 expression and enhancing Smad2 phosphorylation; SRSF4 promotes ca-circFOXP1 biogenesis through FOXP1 pre-mRNA splicing. |
| Confidence score: |
0.8491 |