Interferon-α inducible protein 6 (IFI6) confers protection against ionizing radiation in skin cells

• Published in: Journal of dermatological science 2020-11, Vol.100 (2), p.139-147
• Main Authors: Jia, Huimin, Mo, Wei, Hong, Min, Jiang, Sheng, Zhang, Yuan-Yuan, He, Dan, Yu, Daojiang, Shi, Yuhong, Cao, Jianping, Xu, Xiaohui, Zhang, Shuyu
• Format: Article
• Language: English
• Subjects: Apoptosis; Heat shock response; IFI6; Ionizing radiation; Radiation-induced skin injury
• ISSN: 0923-1811; 1873-569X
• DOI: 10.1016/j.jdermsci.2020.09.003

•Dysregulated transcripts of irradiated human skin keratinocytes were identified by Microarray-based expression profiling.•These dysregulated transcripts were implicated in multiple pathways including type I interferon-mediated pathways.•Interferon α inducible protein 6 (IFI6) is induced by radiation in human skin cells and confers radio protection.•IFI6 is translocated into nucleus and regulating the transcriptional activity of HSF1. 5. A certain amount of potential HSF1-targeted genes upregulated by IFI6 overexpression post radiation is involved. Radiation-induced skin injury is one of the main adverse effects and a dose-limiting factor of radiotherapy without feasible treatment. The underlying mechanism of this disease is still limited. To investigate the potential molecular pathways and mechanisms of radiation-induced skin injury. mRNA expression profiles were determined by Affymetrix Human HTA2.0 microarray.IFI6 overexpression and knockdown were mediated by lentivirus. The functional changes of skin cells were measured by flow cytometry, ROS probe and Edu probe. Protein distribution was detected by immunofluorescence experiment, and IFI6-interacting proteins were detected by immunoprecipitation (IP) combined with mass spectrometry. The global gene changes in IFI6-overexpressed skin cells after irradiation were detected by RNA-seq. mRNA expression profiling showed 50 upregulated and 13 down regulated genes and interferon alpha inducible protein 6 (IFI6) was top upregulated. Overexpression of IFI6 promoted cell proliferation and reduced cell apoptosis as well as ROS production following radiation, and conversely, increased the radiosensitivity of HaCaT and human skin fibroblast (WS1). IFI6 was translocated into nucleus in irradiated skin cells and the interacting relationship with mitochondrial single-stranded DNA-binding protein 1 (SSBP1), which could enhance the transcriptional activity of heat shock transcription factor 1 (HSF1).IFI6 augmented HSF1 activity following radiation in HaCaT and WS1 cells. RNA-seq analysis showed IFI6 modulated virus infection and cellular response to stress pathways, which may help to further explore how IFI6 regulate the transcriptional activity of HSF1. This study reveals that IFI6 is induced by ionizing radiation and confers radioprotection in skin cells.