| Expression pattern: |
UP |
| Associated gene: |
ubiquitin specific peptidase 30 (USP30), HSP90A, signal transducer and activator of transcription 3 (STAT3), c-Myc, MMP2, MMP9, programmed cell death ligand 1 (PD-L1), programmed cell death 1 (PD-1) |
| Associated microRNA: |
miR-424-5p |
| Biological function: |
Circ-HSP90A promotes NSCLC cell proliferation, migration, invasion, stemness, and immune evasion, and promotes CD8 + T cells apoptosis through PD-L1. |
| Molecular mechanism: |
Circ-HSP90A recruits USP30 to de-ubiquitinate and stabilize HSP90A protein, thereby activating STAT3 signaling; it also acts as a miR-424-5p sponge to up-regulate PD-L1 and promote PD-1/PD-L1 checkpoint-mediated immune evasion. |
| Biological pathway or process: |
JAK/STAT (promotes); proliferation (promotes); migration (promotes); invasion (promotes); stemness (promotes); immune regulation (promotes); apoptosis (promotes); ceRNA regulation (promotes); ubiquitination (inhibits) |
| Detected method: |
Q
|
| Validation methods: |
Back-Splice Junction PCR / divergent primers PCR; RNase R Treatment; Actinomycin D / DRB Stability Assay; RT-qPCR; Transfection; CCK8; Colony Formation Assay; Wound Healing Assay; Transwell Assay; Luciferase Reporter Assay; Western Blot; RNA Pull-Down; RIP (RNA Immunoprecipitation); Flow Cytometry(Non-apoptosis/cycle); Nuclear-Cytoplasmic Fractionation; FISH / smFISH; Bioinformatics Analysis |
| Clinical significance: |
Targeting circ-HSP90A might become a novel target of immunotherapy in NSCLC. |
| Description: |
In this study, hsa_circ_0033393/circ-HSP90A is an HSP90A-derived circRNA up-regulated in NSCLC cells. It promotes proliferation, migration, invasion, stemness, and immune evasion by recruiting USP30 to stabilize HSP90A and activate STAT3 signaling, and by sponging miR-424-5p to increase PD-L1 expression and suppress CD8 + T-cell activity. |
| Confidence score: |
0.8093 |