LINC00659 regulates HSP90-IKKα interaction to activate NF-κB signaling and promote glioma invasion
Lijuan Du1, Heping Dong2, Sunmei Cai1
1Department of Radiology, Shanghai Punan Hospital of Pudong New District, Shanghai, China.
Background:
Invasiveness of tumor cells constitutes a major obstacle in glioma treatment. While LINC00659 has been implicated in cancer progression, its specific role and underlying mechanisms in glioma remain unclear.
Methods:
LINC00659 expression in glioma cells was assessed via qPCR. Wound healing and Transwell invasion assays evaluated migratory and invasive capacities. Western blot detected alterations in EMT markers and key NF-κB pathway proteins. Molecular docking predicted LINC00659-HSP90 binding, which was validated by RIP and RNA pull-down assays. Co-IP analyzed HSP90-IKKα interaction, while genetic knockdown/overexpression models elucidated the regulatory mechanism of LINC00659 on tumor invasiveness.
Results:
qPCR revealed LINC00659 upregulation in glioma cell lines. Functional assays demonstrated that LINC00659 knockdown repressed migration, invasion, and EMT. Mechanistically, LINC00659 bound to the chaperone HSP90 to stabilize IKKα protein, thereby activating NF-κB signaling. Rescue experiments confirmed the reversion of HSP90 overexpression on the anti-invasive impact of LINC00659 knockdown.
Conclusion:
This study identified LINC00659 as a key promoter of glioma cell migration, invasion, and EMT, suggesting its potential as a target against glioma malignancy.
Related Concept Videos
NF-κB-dependent Signaling Pathway
NF-κB-dependent Signaling Mechanism
The...
PI3K/mTOR/AKT Signaling Pathway
The JAK-STAT Signaling Pathway
Regulation of Angiogenesis and Blood Supply
lncRNA - Long Non-coding RNAs
Interactions Between Signaling Pathways
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...


