UO Mutagenesis and Preventive Oncology, IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy.
Cellular Electron Microscopy Laboratory, Department of Experimental Medicine, University of Genoa, 16132 Genoa, Italy.
Int J Mol Sci. 2021 Jun 28;22(13):6951. doi: 10.3390/ijms22136951.
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.
We performed cell cycle and proliferation assays, ultrastructural analysis of mitochondria architecture, as well as a global analysis of miRNA modulated under µG conditions.
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.
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.
在太空中，重力向量的减少或丧失会极大地影响细胞之间的相互作用。自太空时代开始以来，微重力已被确定为生物医学中的一种信息工具，包括癌症研究。A549 细胞系是一种低三倍体人肺泡基底上皮细胞系，广泛用作肺腺癌模型。据报道，微重力会干扰各种生物系统中的线粒体活性、能量代谢、细胞活力和增殖、化学敏感性、侵袭和细胞及细胞器形态。关于肺癌，有几项研究报告称，微重力能够调节致癌和转移过程。为了研究这些过程，A549 细胞被暴露于模拟微重力（µG）不同时间点。
我们进行了细胞周期和增殖分析、线粒体结构的超微结构分析，以及 µG 条件下调节的全局 miRNA 分析。
A549 细胞暴露于微重力会产生多核细胞、细胞周期失衡、生长抑制和明显的形态学异常，最明显的是线粒体严重受损。全局 miRNA 分析定义了一组与 µG 刺激相关的 miRNA 主要涉及细胞周期调控、细胞凋亡和应激反应。据我们所知，这是首次对暴露于微重力的 A549 进行的全局 miRNA 分析。尽管有这些结果，但不能得出关于 µG 干扰 A549 细胞致癌或转移过程的能力的任何结论。
我们的结果表明，线粒体对 µG 非常敏感。我们认为，线粒体损伤可能反过来触发与细胞周期失衡相关的 miRNA 调节。
