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.

Cancer Letters
|June 8, 2019
PubMed

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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