FOXQ1 regulates senescence-associated inflammation via activation of SIRT1 expression

Pan Wang, Cuicui Lv, Tao Zhang, Junling Liu, Jin Yang, Fangxia Guan, Tianpei Hong

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Cellular senescence is an initial barrier to tumor development that prevents the proliferation of premalignant cells. However, some of the features of senescent cells seem to promote tumor progression via senescence-associated secretory phenotype (SASP). Here, we demonstrated that the protein level of forkhead box Q1 (FOXQ1), which highly overexpresses in several kinds of tumors, was significantly downregulated during both replicative and oncogene-induced senescence. Moreover, overexpression of FOXQ1 delayed senescence, whereas FOXQ1 silence led to premature senescence in human fibroblasts. Furthermore, we identified that FOXQ1 upregulated SIRT1 expression through transcriptional regulation via directly binding to the SIRT1 promoter. Finally, we showed that FOXQ1 remarkably inhibited the replicative senescence through depressing the expression of the inflammatory cytokines interleukin-6 (IL-6) and IL-8 via modulation of SIRT1-NF-κB pathway. In addition, FOXQ1 overexpressed in human esophageal cancer cells and ablation of FOXQ1 restrained the tumourigenic ability of the esophageal cancer cells (EC109 and EC9706) in a mouse xenograft model in vivo. Taken together, these findings uncover a previously unidentified role of FOXQ1 regulating SASP and tumor development at same time.

Original languageEnglish (US)
Pages (from-to)e2946
JournalCell death & disease
Volume8
Issue number7
DOIs
StatePublished - Jul 20 2017
Externally publishedYes

Fingerprint

Inflammation
Cell Aging
Esophageal Neoplasms
Neoplasms
Forkhead Transcription Factors
Phenotype
Interleukin-8
Oncogenes
Heterografts
Interleukin-6
Down-Regulation
Fibroblasts
Cell Proliferation
Cytokines

ASJC Scopus subject areas

  • Immunology
  • Cellular and Molecular Neuroscience
  • Cell Biology
  • Cancer Research

Cite this

FOXQ1 regulates senescence-associated inflammation via activation of SIRT1 expression. / Wang, Pan; Lv, Cuicui; Zhang, Tao; Liu, Junling; Yang, Jin; Guan, Fangxia; Hong, Tianpei.

In: Cell death & disease, Vol. 8, No. 7, 20.07.2017, p. e2946.

Research output: Contribution to journalArticle

Wang, P, Lv, C, Zhang, T, Liu, J, Yang, J, Guan, F & Hong, T 2017, 'FOXQ1 regulates senescence-associated inflammation via activation of SIRT1 expression', Cell death & disease, vol. 8, no. 7, pp. e2946. https://doi.org/10.1038/cddis.2017.340
Wang, Pan ; Lv, Cuicui ; Zhang, Tao ; Liu, Junling ; Yang, Jin ; Guan, Fangxia ; Hong, Tianpei. / FOXQ1 regulates senescence-associated inflammation via activation of SIRT1 expression. In: Cell death & disease. 2017 ; Vol. 8, No. 7. pp. e2946.
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