Journal article

Authors list: Karger, Annika; Mansouri, Siavash; Leisegang, Matthias S.; Weigert, Andreas; Guenther, 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; Gattenloehner, Stefan; Grimminger, Friedrich; Seeger, Werner; Pullamsetti, Soni Savai; Savai, Rajkumar

Publication year: 2023

Journal: The EMBO Journal

Volume number: 42

Issue number: 18

ISSN: 0261-4189

eISSN: 1460-2075

Open access status: Hybrid

DOI Link: https://doi.org/10.15252/embj.2022111620

Publisher: EMBO Press

Abstract: 
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.

Harvard Citation style: Karger, A., Mansouri, S., Leisegang, M., Weigert, A., Guenther, S., Kuenne, C., et al. (2023) ADPGK-AS1 long noncoding RNA switches macrophage metabolic and phenotypic state to promote lung cancer growth, The EMBO Journal, 42(18). https://doi.org/10.15252/embj.2022111620

APA Citation style: Karger, A., Mansouri, S., Leisegang, M., Weigert, A., Guenther, S., Kuenne, C., Wittig, I., Zukunft, S., Klatt, S., Aliraj, B., Klotz, L., Winter, H., Mahavadi, P., Fleming, I., Ruppert, C., Witte, B., Alkoudmani, I., Gattenloehner, S., Grimminger, F., ...Savai, R. (2023). ADPGK-AS1 long noncoding RNA switches macrophage metabolic and phenotypic state to promote lung cancer growth. The EMBO Journal. 42(18). https://doi.org/10.15252/embj.2022111620