| Expression pattern: |
UP |
| Associated gene: |
GRP78, YTHDF1 |
| Associated microRNA: |
- |
| Biological function: |
circTNIK promotes CNTs-induced malignant transformation, cell proliferation, migration, invasion, tumor growth, malignant lung lesions, M2 macrophage recruitment, and suppression of CD8+ T-cell infiltration and IFN-I-mediated antitumor immunity. |
| Molecular mechanism: |
METTL14-mediated m6A modification enhances circTNIK stability through YTHDF1; circTNIK directly binds GRP78, disrupts GRP78-UPR sensor interactions, activates ER stress, promotes GRP78 nuclear translocation, and suppresses NF-kappaB/IRF3-dependent IFN-I antitumor signaling through GRP78 competitive binding to ID2. |
| Biological pathway or process: |
proliferation (promotes); migration (promotes); invasion (promotes); STING/IFN (inhibits); NF-kappaB (inhibits); immune regulation (inhibits); macrophage polarization (promotes); m6A modification (other); mRNA stability (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; FISH / smFISH; Nuclear-Cytoplasmic Fractionation; Clinical Sample Validation; RIP (RNA Immunoprecipitation); RNA Pull-Down; Co-IP; MeRIP / MeRIP-seq; Transfection; CCK8; Colony Formation Assay; Wound Healing Assay; Transwell Assay; In Vivo Animal Model; IHC (Immunohistochemistry); IF (Immunofluorescence); ELISA; Western Blot; Flow Cytometry（Non-apoptosis/cycle）; Bioinformatics Analysis |
| Clinical significance: |
circTNIK is highly expressed in clinical lung cancer tissues, positively correlates with GRP78 expression, negatively correlates with T-cell infiltration and IFN-I signaling intensity, and may serve as a biomarker and therapeutic target for environmental-exposure-related lung cancer. |
| Description: |
circTNIK is an upregulated human circRNA derived from TNIK in CNTs-induced lung malignant transformation and clinical lung cancer tissues. It promotes malignant phenotypes by binding GRP78 to activate ER stress and by driving GRP78-dependent suppression of NF-kappaB/IRF3-mediated IFN-I antitumor immunity. Its expression is enhanced by METTL14/YTHDF1-mediated m6A regulation, and it may have biomarker and therapeutic-target value in environmental-exposure-related lung cancer. |
| Confidence score: |
0.8861 |