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Updated: Jan 23, 2026

Development of Compendium for Esophageal Squamous Cell Carcinoma
Published on: April 12, 2024
Interferon-inducible lncRNA IRF1-AS represses esophageal squamous cell carcinoma by promoting interferon response
Jianbing Huang1, Jiagen Li1, Yuan Li1
1Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
Abstract:
Interferons (IFNs) play crucial roles in the development and treatment of cancer. Long non-coding RNAs (lncRNAs) are emerging molecules involved in cancer progression. Here, we identified and characterized an IFN-inducible nuclear lncRNA IRF1-AS (Interferon Regulatory Factor 1 Antisense RNA) which was positively correlated with IRF1 expression. IFNs upregulate IRF1-AS via the JAK-STAT pathway. Knockdown and overexpression of IRF1-AS revealed that IRF1-AS inhibits oesophageal squamous cell carcinoma (ESCC) proliferation and promotes apoptosis in vitro and in vivo. Mechanistically, IRF1-AS activates IRF1 (Interferon Regulatory Factor 1) transcription through interacting with ILF3 (Interleukin Enhancer Binding Factor 3) and DHX9 (DExH-Box Helicase 9). In turn, IRF1 binds to the IRF1-AS promoter directly and activates IRF1-AS transcription. Global analysis of IRF1-AS-regulated genes indicated that IRF1-AS activates the IFN response in vitro and in vivo. IRF1 knockdown in IRF1-AS-overexpressing cells abolished the antiproliferative effect and activation of the IFN response. Furthermore, IRF1-AS was downregulated in ESCC tissues, and low expression correlated with poor prognosis. In conclusion, the interferon-inducible lncRNA IRF1-AS represses esophageal squamous cell carcinoma progression by promoting interferon response through a positive regulatory loop with IRF1.
Insights
The interferon-inducible long non-coding RNA IRF1-AS inhibits esophageal squamous cell carcinoma (ESCC) by activating the interferon response. This lncRNA forms a positive feedback loop with IRF1, suppressing tumor growth and improving prognosis.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- Interferons (IFNs) are critical in cancer development and treatment.
- Long non-coding RNAs (lncRNAs) are increasingly recognized for their roles in cancer progression.
Purpose of the Study:
- To identify and characterize novel interferon-inducible lncRNAs involved in esophageal squamous cell carcinoma (ESCC).
- To elucidate the mechanism by which IRF1-AS regulates ESCC proliferation and apoptosis.
Main Methods:
- Identification and characterization of IRF1-AS, a novel IFN-inducible lncRNA.
- Investigated the JAK-STAT pathway's role in IFN-mediated IRF1-AS upregulation.
- Utilized knockdown and overexpression studies in vitro and in vivo.
- Explored the interaction of IRF1-AS with ILF3 and DHX9 to regulate IRF1 transcription.
- Analyzed global gene expression and patient prognosis data.
Main Results:
- IRF1-AS expression is positively correlated with IRF1 and upregulated by IFNs via the JAK-STAT pathway.
- IRF1-AS inhibits ESCC proliferation and promotes apoptosis by activating IRF1 transcription through interaction with ILF3 and DHX9.
- A positive feedback loop exists where IRF1 also enhances IRF1-AS transcription.
- IRF1-AS activates the IFN response and its knockdown abolishes the anti-proliferative effects.
- IRF1-AS is downregulated in ESCC tissues, correlating with poor prognosis.
Conclusions:
- The novel lncRNA IRF1-AS acts as a tumor suppressor in ESCC by enhancing the interferon response through a positive regulatory loop with IRF1.
- IRF1-AS represents a potential therapeutic target for esophageal squamous cell carcinoma.
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