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Published on: October 17, 2025

RNF183 Induces Polarization of M2 Macrophages by Regulating Ubiquitination of PML and Promotes Lung Cancer

Lu Xu1, Chenlin Lu1

  • 1Department of Respiratory Medicine, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou School of Clinical Medicine, Nanjing Medical University, China.

Current Medicinal Chemistry
|July 16, 2026
PubMed
Abstract

Insights

RING finger 183 (RNF183) drives lung cancer progression by promoting M2 macrophage polarization. This occurs through RNF183-mediated ubiquitination of the promyelocytic leukemia (PML) protein, impacting tumor growth and invasion.

Area of Science:

  • Immunology
  • Oncology
  • Molecular Biology

Background:

  • Macrophage polarization significantly influences lung cancer development.
  • M2 macrophages are implicated in accelerating lung cancer progression.

Purpose of the Study:

  • To elucidate the mechanism by which M2 macrophages promote lung cancer progression.
  • To investigate the role of RING finger 183 (RNF183) in M2 macrophage polarization and lung cancer growth.

Main Methods:

  • THP-1 cells were differentiated into M2 macrophages using IL-4/IL-13.
  • Co-culture systems with lung cancer cells and M2 macrophage-conditioned medium were established.
  • Techniques included flow cytometry, qPCR, western blots, CCK-8, clone formation, wound healing, transwell, co-immunoprecipitation, and cycloheximide assays to study RNF183 and PML interactions.

Main Results:

  • RNF183 was identified as a key regulator of M2 macrophage polarization.
  • RNF183 enhances lung cancer cell proliferation, migration, and invasion by stimulating M2 polarization.
  • Mechanistically, RNF183 targets PML for ubiquitination, down-regulating PML and promoting M2 polarization; RNF183 knockdown inhibited cancer progression, which was reversed by PML knockdown.

Conclusions:

  • RNF183 is a novel regulator of M2 macrophage polarization in lung cancer.
  • The RNF183/PML axis, involving ubiquitination, influences macrophage phenotype and the tumor microenvironment.
  • Targeting the RNF183/PML pathway presents a potential immunomodulatory strategy for lung cancer treatment.
Keywords:
Lung cancerM2 macrophagesPMLRNF183ubiquitination

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