FOXQ1 regulates senescence-associated inflammation via activation of SIRT1 expression.

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.

journal_name

Cell Death Dis

journal_title

Cell death & disease

authors

Wang P,Lv C,Zhang T,Liu J,Yang J,Guan F,Hong T

doi

10.1038/cddis.2017.340

subject

Has Abstract

pub_date

2017-07-20 00:00:00

pages

e2946

issue

7

issn

2041-4889

pii

cddis2017340

journal_volume

8

pub_type

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