Cancer Letters

Cancer Letters

Volume 459, 10 September 2019, Pages 86-99
Cancer Letters

Original Articles
Interferon-inducible lncRNA IRF1-AS represses esophageal squamous cell carcinoma by promoting interferon response

https://doi.org/10.1016/j.canlet.2019.05.038Get rights and content
Under a Creative Commons license
open access

Highlights

  • IRF1-AS is a downregulated tumor suppressive lncRNA in ESCC whose low expression predicts poor prognosis.

  • IRF1-AS is induced by IFNs through JAK-STAT pathway which in turn activates IFN response.

  • IRF1-AS and IRF1 form a positive regulatory loop through mutual transcriptional activation.

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.

Keywords

Long non-coding RNA
Interferon
IRF1-AS
IRF1
Esophageal squamous cell carcinoma

Abbreviations

lncRNA
long non-coding RNA
IFN
interferon
IRF1
interferon regulatory factor 1
IRF1-AS
interferon regulatory factor 1 antisense RNA
DHX9
DExH-Box Helicase 9
ILF3
Interleukin Enhancer Binding Factor 3
ESCC
esophageal squamous cell carcinoma
shRNA
Short hairpin RNA
siRNA
Short interfering RNA
ChIP
chromatin immunoprecipitation
Co-IP
Co-Immunoprecipitation
RIP
RNA immunoprecipitation
RACE
rapid amplification of cDNA ends

Cited by (0)

1

Jie He will handle correspondence at all stages of refereeing and publication, also post-publication.