| Expression pattern: |
UP |
| Associated gene: |
METTL3, RBMX, EIF4A3, YAP1, FYN, STAT3, AGO2, PTK2 pre-mRNA |
| Associated microRNA: |
miR-484, miR-125a-3p |
| Biological function: |
circPTK2-m + promotes fibroblast activation, fibroblast proliferation, migration, extracellular matrix/fibrotic marker expression, and pulmonary fibrosis; silencing circPTK2-m + or disrupting m6A methylation attenuates fibroblast activation and alleviates fibrosis. |
| Molecular mechanism: |
METTL3-mediated m6A modification and RBMX promote circPTK2-m + biogenesis; EIF4A3 facilitates nuclear export; cytoplasmic circPTK2-m + acts as a ceRNA that sequesters miR-484 and miR-125a-3p, derepressing YAP1 and FYN and enhancing STAT3 phosphorylation to drive profibrotic transcription. |
| Biological pathway or process: |
fibrosis (promotes); proliferation (promotes); migration (promotes); ceRNA regulation (promotes); m6A modification (promotes); JAK/STAT (promotes); other pathway/process (promotes) |
| Detected method: |
Q
H
S
|
| Validation methods: |
Back-Splice Junction PCR / divergent primers PCR; RNase R Treatment; Sanger Sequencing; Actinomycin D / DRB Stability Assay; RT-qPCR; RNA-seq; MeRIP / MeRIP-seq; RIP (RNA Immunoprecipitation); RNA Pull-Down; FISH / smFISH; Nuclear-Cytoplasmic Fractionation; Luciferase Reporter Assay; Transfection; EdU Staining; Wound Healing Assay; IF (Immunofluorescence); IHC (Immunohistochemistry); H&E Staining; Western Blot; In Vivo Animal Model; Clinical Sample Validation; Bioinformatics Analysis |
| Clinical significance: |
circPTK2-m + is upregulated in PF patient serum and lung tissues and is proposed as a promising therapeutic target for PF intervention. |
| Description: |
circPTK2, especially its m6A-modified form circPTK2-m +, is upregulated in pulmonary fibrosis and acts as a fibroblast-specific profibrotic driver. METTL3/RBMX-dependent m6A regulation promotes its generation, EIF4A3 supports its cytoplasmic export, and cytoplasmic circPTK2-m + sponges miR-484 and miR-125a-3p to increase YAP1 and FYN, activate STAT3 signaling, and enhance fibroblast activation and fibrosis. Silencing circPTK2-m + alleviates BLM-induced pulmonary fibrosis, supporting its therapeutic relevance. |
| Confidence score: |
0.886 |