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.
Highlights
The morphological parameters of A549 maintained in μG are essentially stable in the range between 0 and 48 h
We demonstrated that A549 cell exposure to μG is associated with several biochemical and molecular modifications linked to a series of pathological processes
Our experimental findings provide evidence that mitochondria are very sensitive to μG as well detectable by their morphological alterations at TEM
Summary
Gravitational modulations have a great impact on living organisms as all forms of life have evolved from the very beginning under the constant of gravity force G. The reduction or loss of the gravity vector greatly reduces friction, convection, and hydrostatic forces and this condition affects many fundamental functions at the organism, organ, tissue, and cellular level [1]. As microgravity disturbs the interaction between cells and their environment, changes are seen at the cellular and sub-cellular levels involving morphological, immunological, biochemical, metabolic, transduction, and functional changes. Since the beginning of the space-era, back on the past middle century, microgravity has been regarded as an unconventional but extremely informative tool in biology and medicine including cancer research [2]
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