Related Experiment Video
Updated: Aug 5, 2026
08:32
Genome-Wide CRISPR Screen for Unveiling Radiosensitive and Radioresistant Genes
Published on: May 23, 2025
ADAR1 regulates radiosensitivity in ESCC through cIAP2-NF-κB signaling and C16orf46 editing
Liangchao Sun1, Ahmed Ghanim Glayl2, Ming Zhang3
1Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China.
Iscience
|August 4, 2026
Summary
Adenosine deaminase acting on RNA 1 (ADAR1) promotes radioresistance in esophageal squamous cell carcinoma. Inhibiting ADAR1 enhances tumor cell death via pyroptosis and improves radiotherapy response, suggesting ADAR1 as a potential therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Esophageal squamous cell carcinoma (ESCC) often shows resistance to radiotherapy.
- Adenosine deaminase acting on RNA 1 (ADAR1) is an RNA-editing enzyme implicated in cancer progression.
Purpose of the Study:
- To investigate the role of ADAR1 in regulating radiosensitivity in ESCC.
- To explore ADAR1 as a potential therapeutic target for improving radiotherapy efficacy.
Main Methods:
- Analysis of patient samples, ESCC cell lines, and xenograft models.
- Assessment of ADAR1 expression and its correlation with treatment response.
- Investigation of ADAR1 depletion effects on tumor growth, radiosensitivity, and cell death pathways (pyroptosis).
- Transcriptome-wide RNA-editing analysis to identify ADAR1 targets.
Main Results:
- High ADAR1 expression in ESCC correlated with poor response to chemoradiotherapy.
- ADAR1 suppression reduced tumor growth and increased radiosensitivity in vitro and in vivo.
- ADAR1 depletion induced gasdermin E (GSDME)-mediated pyroptosis, sensitizing cells to irradiation.
- C16orf46 was identified as an ADAR1-dependent editing target, with reduced editing contributing to radiosensitization.
- ADAR1 depletion affected cIAP2 and NF-κB signaling, indicating RNA editing-independent mechanisms.
Conclusions:
- ADAR1-dependent RNA editing regulates radiosensitivity in ESCC.
- ADAR1 is a potential therapeutic target for overcoming radiotherapy resistance in esophageal cancer.
Related Concept Videos
01:38Nucleotide Excision Repair
DNA Distortion and Damage
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
01:08Nucleotide Excision Repair
Overview
02:23Abnormal Proliferation
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
02:34Inhibition of Cdk Activity
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
02:36DNA Damage can Stall the Cell Cycle
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...