Serum factor(s) from lung adenocarcinoma patients regulates the molecular clock expression
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ORIGINAL ARTICLE – CANCER RESEARCH
Serum factor(s) from lung adenocarcinoma patients regulates the molecular clock expression Yi Chang1,2 · Chunsong Zhao2,3,4 · Hui Ding2,3 · Ting Wang2,3 · Caixia Yang2,3 · Xiuhong Nie1 · Yanning Cai2,3,4 Received: 26 May 2020 / Accepted: 11 November 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Lung cancer is a leading cause of cancer-associated deaths worldwide. Lung cancer may lead to circadian disruption, which could contribute to the development of lung cancer. Recently, several studies using animal models indicated that tumors influence systemic circadian homeostasis in remote tissues. However, it is unclear whether carcinoma of the lungs influences remote circadian rhythm, whether this effect exists in humans, and whether signals from the tumor travel through the blood. In this study, we used a cell-based assay to determine whether serum from patients with lung adenocarcinoma could modulate the molecular clock. We found that the daily oscillation period of Bmal1 was significantly lengthened following treatment with serum from untreated lung adenocarcinoma patients. In addition, heat inactivation of this serum abolished the effect, suggesting that a heat-sensitive circulating factor(s) is present in the serum of untreated lung adenocarcinoma patients. Using real-time PCR, we also examined the mRNA abundance of Bmal1, Cry1, and Per1 in human osteosarcoma u2os cell line, HUVECs and A549 cell lines. The expression of Bmal1 was changed in A549 cells in the presence of sera from lung adenocarcinoma patients. Our study revealed a direct effect of serum from lung adenocarcinoma patients on the molecular clock. Keywords Lung adenocarcinoma · Bmal1 · Period · Bioluminescence · Reporter
Introduction Circadian rhythms consist of biological oscillations with a period of approximately 24 h and influence nearly all aspects of physiology (Chaix et al. 2016). The mammalian circadian system is organized in a hierarchical fashion: the suprachiasmatic nuclei (SCN) of the anterior hypothalamus is the Yi Chang and Chunsong Zhao contributed equally to this work * Yanning Cai [email protected] 1
Department of Respiration, Xuanwu Hospital of Capital Medical University, 45 Changchun Street, Beijing 100053, People’s Republic of China
2
Department of Neurobiology, Xuanwu Hospital of Capital Medical University, 45 Changchun Street, Beijing 100053, People’s Republic of China
3
Key Laboratory for Neurodegenerative Diseases of the Ministry of Education, Beijing 100053, People’s Republic of China
4
National Clinical Research Center for Geriatric Disorders, Beijing 100053, People’s Republic of China
central pacemaker of the circadian rhythm. Ablation of SCN leads to complete circadian disruption in animals. The SCN receives light signals from the external environment and converts these stimuli into signals that are sent all over the body to synchronize circadian rhythms in peripheral cells (Honma 2020). At least some of these signals travel through
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