| Expression pattern: |
UP |
| Associated gene: |
ALKBH5, SOCS2, p-JAK2, p-STAT5 |
| Associated microRNA: |
- |
| Biological function: |
Promotes proliferation, migration, invasion, tumorigenicity and metastasis of NSCLC cells. |
| Molecular mechanism: |
circEML4 is transferred via EVs, binds ALKBH5, reduces its nuclear distribution, increases m6A modification of SOCS2, decreases SOCS2 expression, and activates the JAK-STAT signaling axis. |
| Biological pathway or process: |
JAK/STAT (promotes); m6A modification (promotes); proliferation (promotes); migration (promotes); invasion (promotes); metastasis (promotes); extracellular vesicle (other) |
| Detected method: |
Q
|
| Validation methods: |
RT-qPCR; RNase R Treatment; Actinomycin D / DRB Stability Assay; Back-Splice Junction PCR / divergent primers PCR; Sanger Sequencing; FISH / smFISH; Clinical Sample Validation; RNA Pull-Down; RIP (RNA Immunoprecipitation); Transfection; CCK8; EdU Staining; Colony Formation Assay; Transwell Assay; Western Blot; IHC (Immunohistochemistry); In Vivo Animal Model; H&E Staining; Bioinformatics Analysis |
| Clinical significance: |
circEML4 in EVs from TAMs acts as a diagnostic biomarker for NSCLC, especially for patients with smoking history. |
| Description: |
circEML4 is enriched in EVs from smoking/CSE-induced M2 macrophages and transferred to NSCLC cells. It binds ALKBH5, decreases nuclear ALKBH5, increases SOCS2 m6A modification leading to reduced SOCS2 and activation of JAK/STAT signaling, thereby promoting NSCLC cell proliferation, migration, invasion, tumor growth and metastasis; EV circEML4 is proposed as a diagnostic biomarker especially in smokers. |
| Confidence score: |
0.8624 |