Vesicular Release and Uptake of Circular LSD1-RNAs from Non-Cancer and Cancer Lung Cells.

Autor: Galang JN; Institute of Pathology, University Hospital of Cologne, 50937 Cologne, Germany.; Center for Molecular Medicine Cologne, University of Cologne, 50937 Cologne, Germany., Shen Y; Institute of Pathology, University Hospital of Cologne, 50937 Cologne, Germany.; Center for Molecular Medicine Cologne, University of Cologne, 50937 Cologne, Germany., Koitzsch U; Institute of Pathology, University Hospital of Cologne, 50937 Cologne, Germany.; Center for Molecular Medicine Cologne, University of Cologne, 50937 Cologne, Germany., Yu X; Institute of Pathology, University Hospital of Cologne, 50937 Cologne, Germany.; Center for Molecular Medicine Cologne, University of Cologne, 50937 Cologne, Germany., Eischeid-Scholz H; Institute of Pathology, University Hospital of Cologne, 50937 Cologne, Germany.; Center for Molecular Medicine Cologne, University of Cologne, 50937 Cologne, Germany., Bachurski D; CECAD Center of Excellence on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, 50937 Cologne, Germany.; Department I of Internal Medicine, University Hospital of Cologne, 50937 Cologne, Germany., Rau TT; Institute of Pathology, University Hospital of Duesseldorf, 40225 Duesseldorf, Germany., Neppl C; Institute of Pathology, University Hospital of Duesseldorf, 40225 Duesseldorf, Germany., Herling M; Department I of Internal Medicine, University Hospital of Cologne, 50937 Cologne, Germany.; Department of Hematology, Cellular Therapy and Hemostaseology, University of Leipzig, 04103 Leipzig, Germany., Bulimaga B; Institute of Pathology, University Hospital of Cologne, 50937 Cologne, Germany.; Center for Molecular Medicine Cologne, University of Cologne, 50937 Cologne, Germany., Vasyutina E; Department I of Internal Medicine, University Hospital of Cologne, 50937 Cologne, Germany.; Department of Hematology, Cellular Therapy and Hemostaseology, University of Leipzig, 04103 Leipzig, Germany., Schweiger MR; Center for Molecular Medicine Cologne, University of Cologne, 50937 Cologne, Germany.; Institute for Epigenetics, University Hospital of Cologne, 50937 Cologne, Germany., Büttner R; Institute of Pathology, University Hospital of Cologne, 50937 Cologne, Germany.; Center for Molecular Medicine Cologne, University of Cologne, 50937 Cologne, Germany., Odenthal M; Institute of Pathology, University Hospital of Cologne, 50937 Cologne, Germany.; Center for Molecular Medicine Cologne, University of Cologne, 50937 Cologne, Germany., Anokhina MM; Institute of Pathology, University Hospital of Cologne, 50937 Cologne, Germany.; Center for Molecular Medicine Cologne, University of Cologne, 50937 Cologne, Germany.; Institute of Pathology, University Hospital of Duesseldorf, 40225 Duesseldorf, Germany.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2023 Sep 12; Vol. 24 (18). Date of Electronic Publication: 2023 Sep 12.
DOI: 10.3390/ijms241813981
Abstrakt: Lysine-specific demethylase 1 (LSD1) is highly expressed in many cancer types and strongly associated with cancer progression and metastasis. Circular RNAs (circRNAs) are produced by back-splicing and influence the interactive RNA network by microRNA and protein sponging. In the present study, we aimedto identify circRNAs that derive from the LSD1-encoding KDM1A gene, and to investigate their potential to be released and uptaken by lung cancer versus non-cancer epithelial cells. We identified four circLSD1-RNAs by RT-PCR with divergent primers, followed by sequencing. The expression level of circLSD1-RNAs was then studied by quantitative PCR on cellular and extracellular fractions of lung cancer (PC9) and non-cancer primary small airway epithelial (PSAE) cells. Moreover, we established the transgenic overexpression of circLSD1-RNAs. We show that circLSD1-RNAs are primarily located in the cytoplasm, but are packaged and released from lung cancer and non-cancer cells by extracellular vesicles (EVs) and ribonucleoprotein (RNP) complexes, respectively. Proteomics demonstrated a different protein pattern of EV fractions released from PC9 versus PSAE cells. Importantly, released circLSD1-RNAs were differently taken up by PSAE and PC9 cells. In conclusion, our findings provide primary evidence that circLSD1-RNAs participate in the intercellular communication of lung cancer cells with the tumor environment.
Databáze: MEDLINE
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