Paolo Degan1, Katia Cortese2, Alessandra Pulliero3, Silvia Bruno4, Maria Cristina Gagliani2, Matteo Congiu4, Alberto Izzotti1,4. 1. UO Mutagenesis and Preventive Oncology, IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy. 2. Cellular Electron Microscopy Laboratory, Department of Experimental Medicine, University of Genoa, 16132 Genoa, Italy. 3. Department of Health Sciences, Department of Health Sciences University of Genoa, 16132 Genoa, Italy. 4. Department of Experimental Medicine, University of Genoa, 16132 Genoa, Italy.
Abstract
BACKGROUND: In space, the reduction or loss of the gravity vector greatly affects the interaction between cells. Since the beginning of the space age, microgravity has been identified as an informative tool in biomedicine, including cancer research. The A549 cell line is a hypotriploid human alveolar basal epithelial cell line widely used as a model for lung adenocarcinoma. Microgravity has been reported to interfere with mitochondrial activity, energy metabolism, cell vitality and proliferation, chemosensitivity, invasion and morphology of cells and organelles in various biological systems. Concerning lung cancer, several studies have reported the ability of microgravity to modulate the carcinogenic and metastatic process. To investigate these processes, A549 cells were exposed to simulated microgravity (µG) for different time points. METHODS: We performed cell cycle and proliferation assays, ultrastructural analysis of mitochondria architecture, as well as a global analysis of miRNA modulated under µG conditions. RESULTS: The exposure of A549 cells to microgravity is accompanied by the generation of polynucleated cells, cell cycle imbalance, growth inhibition, and gross morphological abnormalities, the most evident are highly damaged mitochondria. Global miRNA analysis defined a pool of miRNAs associated with µG solicitation mainly involved in cell cycle regulation, apoptosis, and stress response. To our knowledge, this is the first global miRNA analysis of A549 exposed to microgravity reported. Despite these results, it is not possible to draw any conclusion concerning the ability of µG to interfere with the cancerogenic or the metastatic processes in A549 cells. CONCLUSIONS: Our results provide evidence that mitochondria are strongly sensitive to µG. We suggest that mitochondria damage might in turn trigger miRNA modulation related to cell cycle imbalance.
BACKGROUND: In space, the reduction or loss of the gravity vector greatly affects the interaction between cells. Since the beginning of the space age, microgravity has been identified as an informative tool in biomedicine, including cancer research. The A549 cell line is a hypotriploid human alveolar basal epithelial cell line widely used as a model for lung adenocarcinoma. Microgravity has been reported to interfere with mitochondrial activity, energy metabolism, cell vitality and proliferation, chemosensitivity, invasion and morphology of cells and organelles in various biological systems. Concerning lung cancer, several studies have reported the ability of microgravity to modulate the carcinogenic and metastatic process. To investigate these processes, A549 cells were exposed to simulated microgravity (µG) for different time points. METHODS: We performed cell cycle and proliferation assays, ultrastructural analysis of mitochondria architecture, as well as a global analysis of miRNA modulated under µG conditions. RESULTS: The exposure of A549 cells to microgravity is accompanied by the generation of polynucleated cells, cell cycle imbalance, growth inhibition, and gross morphological abnormalities, the most evident are highly damaged mitochondria. Global miRNA analysis defined a pool of miRNAs associated with µG solicitation mainly involved in cell cycle regulation, apoptosis, and stress response. To our knowledge, this is the first global miRNA analysis of A549 exposed to microgravity reported. Despite these results, it is not possible to draw any conclusion concerning the ability of µG to interfere with the cancerogenic or the metastatic processes in A549 cells. CONCLUSIONS: Our results provide evidence that mitochondria are strongly sensitive to µG. We suggest that mitochondria damage might in turn trigger miRNA modulation related to cell cycle imbalance.
Entities:
Keywords:
A549 cell; electron microscopy; lung cancer; microRNA; microgravity; mitochondria
Authors: José Luis Cortés-Sánchez; Jonas Callant; Marcus Krüger; Jayashree Sahana; Armin Kraus; Bjorn Baselet; Manfred Infanger; Sarah Baatout; Daniela Grimm Journal: Biomedicines Date: 2021-12-23
Authors: Daniela Grimm; Herbert Schulz; Marcus Krüger; José Luis Cortés-Sánchez; Marcel Egli; Armin Kraus; Jayashree Sahana; Thomas J Corydon; Ruth Hemmersbach; Petra M Wise; Manfred Infanger; Markus Wehland Journal: Int J Mol Sci Date: 2022-03-12 Impact factor: 5.923