Enhancing the anti-breast tumour activity of STING through a novel sting transcriptional regulator

Abstract Background STING (STimulator of INterferon Genes) is a pattern recognition receptor detecting cytoplasmic nucleic acids and transmits signals that activate host innate immune responses. It has been found to be involved in anti‐microbial immunity, autoimmune disorder and tumorigenesis. Thus, the acknowledgement of the cellular regulation of STING is important. However, transcriptional regulation of STING and its role in tumor development has not been reported. Methods STNF expressing vector was constructed and used to identify the STNF regulatory function of STING. Small interfering RNA was used to silence STNF expression. For the first time, full length of STING promoter was constructed with luciferase reporter which enabled quick and semi-quantitative of STING promoter activity. The bc-GenExMiner v4.2 database was used to evaluate the expression and prognostic merit of STNF and STING in breast cancer (BC). Western blot, RT-qPCR and CCK-8 assay were used to detect STING expression and BC cell growth. Results We have identified a novel negative regulator of STING (STNF). The effect of STNF appeared to be at the transcriptional level of STING since STNF could suppress the promoter activity of STING. STNF was up-regulated in breast cancer (BC) and associated with poor prognosis of BC patients. Silencing STNF or pharmacologically inhibiting STNF promoted STING expression and suppressed BC growth. STING down-regulation was observed in different types of BC and restoration of STING expression resulted in broad BC inhibition. Conclusions Our study demonstrated an unprecedented strategy used by breast tumor to escape from STING mediated tumor suppression. The identification of a novel STING regulator will provide insights for novel anti-tumor strategy against BC. Legal entity responsible for the study Xiao-Fang Yu. Funding National Youth Science Fund Project: 81701988(C0025181). Disclosure All authors have declared no conflicts of interest.