The role and mechanism of ARRB1 in simulated space radiation and microgravity-induced lung carcinogenesis

Microgravity can exacerbate radiation-induced DNA damage response, suggesting that microgravity may increase the risk of tumor initiation and development. However, the specific mechanism is still unclear. This study used X-rays, protons, and carbon ions to simulate space radiation, and three-dimensional clinostats or hind limb unloading to simulate microgravity. It was found that simulated space radiation and/or microgravity promoted malignant transformation and tumor development of lung epithelial cells BEAS-2B, and the two factors showed a synergistic effect. The mechanism involves simulated space radiation and/or microgravity leads to changes in intracellular calcium ion concentration, affecting cellular signaling pathways, inducing the interaction between CAMK2G and ARRB1, and promoting ARRB1 nuclear translocation. ARRB1 nuclear translocation enhances CA9 transcriptional activity following simulated space radiation and/or microgravity exposure. In short, changes in intracellular calcium concentration play a crucial role in ARRB1 nuclear translocation and subsequent malignant transformation.