Details

Autor(en) / Beteiligte

• Karger, Annika
• Mansouri, Siavash
• Leisegang, Matthias S
• Weigert, Andreas
• Günther, Stefan
• Kuenne, Carsten
• Wittig, Ilka
• Zukunft, Sven
• Klatt, Stephan
• Aliraj, Blerina
• Klotz, Laura V
• Winter, Hauke
• Mahavadi, Poornima
• Fleming, Ingrid
• Ruppert, Clemens
• Witte, Biruta
• Alkoudmani, Ibrahim
• Gattenlöhner, Stefan
• Grimminger, Friedrich
• Seeger, Werner
• Pullamsetti, Soni Savai
• Savai, Rajkumar

Titel

ADPGK-AS1 long noncoding RNA switches macrophage metabolic and phenotypic state to promote lung cancer growth

Ist Teil von

• The EMBO journal, 2023-09, Vol.42 (18), p.e111620-e111620

Ort / Verlag

England: Blackwell Publishing Ltd

Erscheinungsjahr

2023

Quelle

Wiley-Blackwell Journals

Beschreibungen/Notizen

• Long noncoding RNAs (lncRNAs) influence the transcription of gene networks in many cell types, but their role in tumor-associated macrophages (TAMs) is still largely unknown. We found that the lncRNA ADPGK-AS1 was substantially upregulated in artificially induced M2-like human macrophages, macrophages exposed to lung cancer cells in vitro, and TAMs from human lung cancer tissue. ADPGK-AS1 is partly located within mitochondria and binds to the mitochondrial ribosomal protein MRPL35. Overexpression of ADPGK-AS1 in macrophages upregulates the tricarboxylic acid cycle and promotes mitochondrial fission, suggesting a phenotypic switch toward an M2-like, tumor-promoting cytokine release profile. Macrophage-specific knockdown of ADPGK-AS1 induces a metabolic and phenotypic switch (as judged by cytokine profile and production of reactive oxygen species) to a pro-inflammatory tumor-suppressive M1-like state, inhibiting lung tumor growth in vitro in tumor cell-macrophage cocultures, ex vivo in human tumor precision-cut lung slices, and in vivo in mice. Silencing ADPGK-AS1 in TAMs may thus offer a novel therapeutic strategy for lung cancer.