Related Experiment Video
Updated: Apr 18, 2026
Characterization of Functionally Associated miRNAs in Glioblastoma and their Engineering into Artificial Clusters for Gene Therapy
Published on: October 4, 2019
DNA damage-induced NF-κB activation in human glioblastoma cells promotes miR-181b expression and cell proliferation
Rui-Xue Xu1, Rong-Yao Liu, Chun-Ming Wu
1Department of Neurosurgery, the First Affiliated Hospital of Dalian Medical University, Dalian, China.
Background:
Glioblastoma (GBM) is the most common and most aggressive form of brain cancer. After surgery, radiotherapy is the mainstay of treatment for GBM patients. Unfortunately, the vast majority of GBM patients fail responding to radiotherapy because GBM cells remain highly resistant to radiation. Radiotherapy-induced DNA damage response may correlate with therapeutic resistance.
Methods:
Ionizing radiation (IR) was used to induce DNA damage. Cell proliferation and migration were detected by wound-healing, MTT and apoptosis assays. Dual-luciferase assays and Western blot analysis were performed to evaluate NF-κB activation and validate microRNA targets. Real-time PCR was used to study mRNA and microRNA levels.
Results:
IR-induced DNA damage activated NF-κB in GBM cells which promoted expression of IL-6, IL-8 and Bcl-xL, thereby contributing to cell survival and invasion. Knockdown SENP2 expression enhanced NF-κB essential modulator (NEMO) SUMOylation and NF-κB activity following IR exposure. miR-181b targets SENP2 and positively regulated NF-κB activity.
Conclusion:
NF-κB activation by DNA damage in GBM cells confers resistance to radiation-induced death.
Insights
Glioblastoma cells resist radiotherapy due to DNA damage activating NF-κB. This pathway promotes cell survival and invasion, highlighting a key mechanism of treatment failure in brain cancer.
Area of Science:
- Neuro-oncology
- Cancer biology
- Molecular oncology
Background:
- Glioblastoma (GBM) is an aggressive brain cancer with poor prognosis.
- Radiotherapy is a primary treatment, but GBM exhibits high intrinsic radioresistance.
- DNA damage response pathways are implicated in GBM radioresistance.
Purpose of the Study:
- Investigate the role of DNA damage response in GBM radioresistance.
- Elucidate the molecular mechanisms underlying NF-κB activation in response to radiation.
- Identify potential therapeutic targets to overcome GBM radioresistance.
Main Methods:
- Induction of DNA damage using ionizing radiation (IR).
- Assessment of cell proliferation, migration, and apoptosis.
- Evaluation of NF-κB activation, target gene expression (IL-6, IL-8, Bcl-xL), and microRNA regulation (miR-181b, SENP2) via luciferase assays, Western blot, and real-time PCR.
Main Results:
- IR-induced DNA damage activates NF-κB in GBM cells.
- Activated NF-κB upregulates IL-6, IL-8, and Bcl-xL, promoting GBM cell survival and invasion.
- SENP2 knockdown enhances NF-κB activity; miR-181b targets SENP2 and positively regulates NF-κB.
Conclusions:
- NF-κB activation by DNA damage is a critical mechanism conferring radioresistance in GBM.
- Targeting the NF-κB pathway or its regulators may sensitize GBM to radiotherapy.
Related Concept Videos
02:26NF-κB-dependent Signaling Pathway
NF-κB-dependent Signaling Mechanism
The...
02:23Abnormal Proliferation
02:26NF-kB-dependent Signaling Pathway
01:24Small GTPases - Ras and Rho
Three regulatory proteins control their activity:
02:36DNA Damage Can Stall the Cell Cycle
02:36DNA Damage can Stall the Cell Cycle