IL-1β induces expression of proinflammatory cytokines and migration of human colon cancer cells through upregulation of SIRT1

Jaekyung Jung, Yeon Hwa Lee, Xizhu Fang, Su Jung Kim, Seong Hoon Kim, Do Hee Kim, Na Young Song, Hye Kyung Na, Jeong Heum Baek, Young Joon Surh

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

SIRT1 is a mammalian NAD+-dependent deacetylase, which is known to be involved in various physiological events, such as adaptive response to environmental stresses including caloric restriction, as well as in aging and cellular senescence. However, recent studies have revealed overexpression of SIRT1 in many different types of human malignancies, particularly colon cancer. Interleukin-1β (IL-1β) is a proinflammatory cytokine that plays a major role in invasiveness, stemness and progression of colon cancer. However, the interaction between IL-1β and SIRT1 in the tumor development and progression remains elusive. In this study, we found that IL-1β induces SIRT1 protein expression in human colon cancer HCT-116 cells. IL-1β-induced SIRT1 upregulation led to enhanced expression of mRNA transcripts of pro-inflammatory cytokines, IL-6 and IL-8 as well as that of IL-1β. Knockdown of SIRT1 prevented IL-1β-induced phosphorylation and nuclear accumulation of c-Jun. Furthermore, pharmacologic inhibition of SIRT1 abrogated clonogenicity and migrative capability of human colon cancer cells stimulated with IL-1β. In summary, IL-1β-induced SIRT1 upregulation stimulates production of proinflammatory cytokines via a nuclear accumulation of c-Jun, leadng to colon cancer growth and progression.

Original languageEnglish
Article number108847
JournalArchives of Biochemistry and Biophysics
Volume703
DOIs
Publication statusPublished - 2021 May 30

Bibliographical note

Funding Information:
This study was supported by the Global Core Research Center (GCRC) grant (No. 2011-0030001 ) and the BK21 FOUR Program ( 5120200513755 ) from the National Research Foundation, Republic of Korea .

Publisher Copyright:
© 2021 Elsevier Inc.

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology

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