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LncRNA625 inhibits STAT1-mediated transactivation potential in esophageal cancer cells

•LncRNA625 inhibits STAT1-mediated transcriptional activation.•LncRNA625 interacts with STAT1.•LncRNA625 promotes STAT1 interaction with TC45. Although Signal transducer and activator of transcription 1 (STAT1)-mediated transactivation potential is inhibited in cancer cells, the mechanism is poorly...

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Published in:The international journal of biochemistry & cell biology 2019-12, Vol.117, p.105626-105626, Article 105626
Main Authors: Guo-Wei, Huang, Chun-Quan, Li, Lian-Di, Liao, Ji-Wei, Jiao, Lin, Long, Ji-Yu, Ding, Jin-Cheng, Guo, En-Min, Li, Li-Yan, Xu
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Language:English
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Summary:•LncRNA625 inhibits STAT1-mediated transcriptional activation.•LncRNA625 interacts with STAT1.•LncRNA625 promotes STAT1 interaction with TC45. Although Signal transducer and activator of transcription 1 (STAT1)-mediated transactivation potential is inhibited in cancer cells, the mechanism is poorly understood. In the present study, we implicated long non-coding RNA lncRNA625 in the inhibition of STAT1 activity. LncRNA625 knockdown up-regulated STAT1-mediated transcription and resulted in an increase of STAT1-mediated expression of IFITM2. Conversely, lncRNA625 upregulation inhibited STAT1 reporter activity. Mechanistically, lncRNA625 inhibited STAT1 binding to the promoter of IFITM2 in both untreated cells and following interferon-gamma (IFN-γ) stimulation. LncRNA625 interacted with the DNA-binding (DB) domain of STAT1 and promoted STAT1 interaction with T-cell protein tyrosine phosphatase TC45 to dephosphorylate pSTAT1. Taken together, the results show that lncRNA625 inhibits STAT1-mediated transactivation potential by causing formation of STAT1-TC45 complexes, resulting in STAT1 dephosphorylation.
ISSN:1357-2725
1878-5875
DOI:10.1016/j.biocel.2019.105626