Related Experiment Video
Updated: Aug 1, 2025
Author Spotlight: Tracing the Ferroptotic Signatures and Cell Death Dynamics in Medulloblastoma for Advanced Therapeutics
Published on: March 15, 2024
Inhibition of TRF2 Leads to Ferroptosis, Autophagic Death, and Apoptosis by Causing Telomere Dysfunction
Qiuhui Yang1,2, Ziyang Nie1,2,3, Yukun Zhu1,2,4
1Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China.
Background:
Gastric cancer (GC) is an aggressive malignancy with a high mortality rate and poor prognosis. Telomeric repeat-binding factor 2 (TRF2) is a critical telomere protection protein. Emerging evidence indicates that TRF2 may be an essential treatment option for GC; however, the exact mechanism remains largely unknown.
Objective:
We aimed to explore the role of TRF2 in GC cells. The function and molecular mechanisms of TRF2 in the pathogenesis of GC were mainly discussed in this study.
Methods:
Relevant data from GEPIA and TCGA databases regarding TRF2 gene expression and its prognostic significance in GC samples were analyzed. Analysis of 53BP1 foci at telomeres by immunofluorescence, metaphase spreads, and telomere-specific FISH analysis was carried out to explore telomere damage and dysfunction after TRF2 depletion. CCK8 cell proliferation, trypan blue staining, and colony formation assay were performed to evaluate cell survival. Apoptosis and cell migration were determined with flow cytometry and scratch-wound healing assay, respectively. qRT-PCR and Western blotting were carried out to analyze the mRNA and protein expression levels after TRF2 depletion on apoptosis, autophagic death, and ferroptosis.
Results:
By searching with GEPIA and TCGA databases, the results showed that the expression levels of TRF2 were obviously elevated in the samples of GC patients, which was associated with adverse prognosis. Knockdown of TRF2 suppressed the cell growth, proliferation, and migration in GC cells, causing significant telomere dysfunction. Apoptosis, autophagic death, and ferroptosis were also triggered in this process. The pretreatment of chloroquine (autophagy inhibitor) and ferrostatin-1 (ferroptosis inhibitor) improved the survival phenotypes of GC cells.
Conclusion:
Our data suggest that TRF2 depletion can inhibit cell growth, proliferation, and migration through the combined action of ferroptosis, autophagic death, and apoptosis in GC cells. The results indicate that TRF2 might be used as a potential target to develop therapeutic strategies for treating GC.
Insights
Telomeric repeat-binding factor 2 (TRF2) is elevated in gastric cancer, promoting cell growth. Inhibiting TRF2 triggers apoptosis, autophagic death, and ferroptosis, offering a potential therapeutic strategy for gastric cancer.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Gastric cancer (GC) is a highly aggressive malignancy with poor patient prognosis.
- Telomeric repeat-binding factor 2 (TRF2) is crucial for telomere protection.
- Emerging evidence suggests TRF2's potential as a therapeutic target in GC, but its mechanisms are unclear.
Purpose of the Study:
- To investigate the role and molecular mechanisms of TRF2 in gastric cancer pathogenesis.
- To explore the functional significance of TRF2 in GC cell lines.
Main Methods:
- Analysis of TRF2 gene expression and prognostic significance in GC using GEPIA and TCGA databases.
- Assessment of telomere damage and dysfunction via immunofluorescence, metaphase spreads, and FISH after TRF2 depletion.
- Evaluation of cell proliferation, survival, apoptosis, and migration using CCK8, trypan blue, colony formation, flow cytometry, and scratch-wound assays.
- Analysis of mRNA and protein expression related to apoptosis, autophagy, and ferroptosis using qRT-PCR and Western blotting.
Main Results:
- TRF2 expression is significantly elevated in GC tissues and correlates with adverse prognosis.
- TRF2 knockdown inhibits GC cell growth, proliferation, and migration, inducing telomere dysfunction.
- TRF2 depletion triggers apoptosis, autophagic death, and ferroptosis in GC cells.
- Inhibitors of autophagy (chloroquine) and ferroptosis (ferrostatin-1) partially rescue cell survival.
Conclusions:
- TRF2 depletion inhibits GC cell progression via combined ferroptosis, autophagic death, and apoptosis.
- TRF2 represents a potential therapeutic target for developing novel treatment strategies for gastric cancer.
Related Concept Videos
01:16Necrosis
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become...
01:46Electron Transport Chain: Complex I and II
ROS generation is regulated and maintained at moderate levels necessary...
02:15Replicative Cell Senescence
01:30Overview of Cell Death
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the...
02:41Telomeres and Telomerase
01:18Autophagic Cell Death
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and...