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Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo
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CNOT11 depletion is associated with autophagy-related responses and IL-6-JAK-STAT signaling in cancer cells

Saori Nishijima1, Toru Suzuki2, Tadashi Yamamoto1

  • 1Cell Signal Unit, Okinawa Institute of Science and Technology Graduate University, Okinawa, Japan.

Frontiers in Cell and Developmental Biology
|August 1, 2026
PubMed
Abstract

Insights

Depleting CNOT11, a subunit of the CCR4-NOT complex, triggers autophagy and increases IL-6 production. This suggests CNOT11 influences cellular stress responses through the IL-6-JAK-STAT pathway.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Gene Regulation

Background:

  • The CCR4-NOT complex is crucial for mRNA decay.
  • The function of the vertebrate-specific subunit CNOT11 is not well understood.
  • Investigating CNOT11's role in cellular stress is important for understanding gene regulation.

Purpose of the Study:

  • To elucidate the role of CNOT11 in cellular stress responses.
  • To determine the impact of CNOT11 depletion on mRNA decay and related pathways.
  • To explore the connection between CNOT11, autophagy, and inflammatory signaling.

Main Methods:

  • siRNA-mediated knockdown of CNOT11.
  • Analysis of CCR4-NOT complex composition via immunoprecipitation.
  • Transcriptomic analysis, quantitative RT-PCR, and ELISA for gene expression.
  • Assessment of autophagy markers (LC3-II) and signaling pathways (AMPK, ULK1, JAK-STAT).

Main Results:

  • CNOT11 depletion reduced CNOT10 association with the CCR4-NOT complex.
  • Knockdown led to LC3-II accumulation and upregulation of autophagy-related genes.
  • Increased IL-6 expression and secretion were observed, with enhanced STAT1/STAT3 phosphorylation.
  • IL-6 and STAT3 signaling partially mediated the observed LC3-II accumulation.

Conclusions:

  • CNOT11 depletion impacts cellular stress responses, including autophagy induction.
  • IL-6-JAK-STAT signaling plays a partial role in the CNOT11 depletion phenotype.
  • Further studies are needed to fully characterize autophagic flux and IL-6 signaling causality.
Keywords:
CCR4-NOT complex (CNOT)CNOT11IL-6JAK-STAT signalingautophagy-related responseslysosome

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