Interferon-inducible lncRNA IRF1-AS represses esophageal squamous cell carcinoma by promoting interferon response. (10th September 2019)

• Record Type: Journal Article
• Authors: Huang, Jianbing; Li, Jiagen; Li, Yuan; Lu, Zhiliang; Che, Yun; Mao, Shuangshuang; Lei, Yuanyuan; Zang, Ruochuan; Zheng, Sufei; Liu, Chengming; Wang, Xinfeng; Li, Ning; Sun, Nan; He, Jie
• Is Part Of: Cancer letters. Volume 459(2019)
• Page Start: 86
• Page End: 99
• Publication Date: 2019-09-10
• Subjects: Long non-coding RNA -- Interferon -- IRF1-AS -- IRF1 -- Esophageal squamous cell carcinoma; 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; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2019.05.038
• Languages: English
• ISSNs: 0304-3835

Abstract

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. 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.