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. Micrograv-ity 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 micro-gravity is accompanied by the generation of polynucleated cells, cell cycle imbalance, growth inhi-bition, 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 meta-static 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.

Simulated microgravity effects on human adenocarcinoma alveolar epithelial cells: Characterization of morphological, functional and epigenetic parameters

Degan P.;Cortese K.;Pulliero A.;Bruno S.;Gagliani M. C.;Congiu M.;Izzotti A.
2021-01-01

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. Micrograv-ity 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 micro-gravity is accompanied by the generation of polynucleated cells, cell cycle imbalance, growth inhi-bition, 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 meta-static 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.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11567/1107848
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