Related Experiment Video

Updated: Jul 20, 2025

Activation and Measurement of NLRP3 Inflammasome Activity Using IL-1β in Human Monocyte-derived Dendritic Cells
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Activation and Measurement of NLRP3 Inflammasome Activity Using IL-1β in Human Monocyte-derived Dendritic Cells

Published on: May 22, 2014

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NR1D1 deficiency in the tumor microenvironment promotes lung tumor development by activating the NLRP3 inflammasome

Sun Mi Kim1,2, Yoon Jeon3, Ji Yun Jang3,4

  • 1Graduate School of Cancer Science and Policy, National Cancer Center, Gyeonggi, 10408, Republic of Korea. ksm999@ncc.re.kr.

Cell Death Discovery
|July 31, 2023
PubMed

Insights

Nuclear receptor Rev-erbα (NR1D1) acts as a tumor suppressor in lung cancer by inhibiting the NLRP3 inflammasome. NR1D1 deficiency promotes lung tumorigenesis, suggesting NLRP3 inflammasome blockade as a therapeutic strategy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Circadian Biology

Background:

  • Nuclear receptor Rev-erbα (NR1D1) is a key circadian clock regulator.
  • Its role in cancer development, particularly lung cancer, remains largely unexplored.
  • Circadian clock dysregulation is implicated in various cancers.

Purpose of the Study:

  • To investigate the role of NR1D1 in lung tumorigenesis.
  • To elucidate the underlying mechanisms involving the tumor microenvironment and inflammasome activation.
  • To explore potential therapeutic strategies targeting NR1D1 and the NLRP3 inflammasome.

Main Methods:

  • Utilized genetically engineered mouse models to study Nr1d1 in lung cancer.
  • Assessed NR1D1 effects on non-small cell lung cancer (NSCLC) cell proliferation in vitro.
  • Investigated NR1D1's impact on the tumor microenvironment using orthotopic models.
  • Analyzed NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) inflammasome activation.
  • Evaluated the effects of conditioned medium from NR1D1-deficient macrophages on cancer cells.
  • Tested the efficacy of MCC950, an NLRP3 inflammasome inhibitor, in preclinical models.

Main Results:

  • NR1D1 deficiency in the tumor microenvironment accelerated lung cancer development in an orthotopic model.
  • NR1D1-deficient mice exhibited heightened NLRP3 inflammasome activation.
  • Conditioned medium from NR1D1-deficient macrophages promoted lung cancer cell proliferation and epithelial-mesenchymal transition (EMT).
  • MCC950 treatment significantly inhibited tumorigenesis in NR1D1-deficient mice and blocked cancer cell proliferation and EMT in vitro.

Conclusions:

  • NR1D1 functions as a tumor suppressor in the lung cancer microenvironment.
  • NR1D1 negatively regulates the NLRP3 inflammasome pathway.
  • Targeting the NLRP3 inflammasome through NR1D1 activation presents a potential therapeutic avenue for lung cancer treatment.

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