Abstract
Cytoskeletal protein β-actin is abundant both in the cytoplasm and the nucleus, its mRNA is commonly utilized an internal control for gene expression analysis. Recent reports demostrated that hypoxia influences the levels of β-actin in a variety of cells. The mechanism underlying this change are not yet elucidated. In this work, we show that the changes in the levels of hypoxia-induced Nuclear respiratory factor-1 (NRF-1) lead to the change in expression of β-actin. We compared the protein levels of NRF-1 and β-actin in gastric cancer and adjacent tissues and found their significantly upregulation in cancer (33% patitents). When gastric cancer cells and normal gastric cells were treated with 1% O2 for 48 h, the trends in expression levels of NRF-1 and β-actin were similar. When NRF-1 expression was modified by its overexpressing or silencing, the levels of β-actin changed accordingly. In β-actin gene (ACTB), three binding sites for NRF-1 were found. These sites are conserved in human, mouse and rat genomes. In ChIP experiments, we showed that NRF-1 directly binds to human ACTB and mouse Actb coding regions. Its seems that the transcription of β-actin encoding gene is NRF-1 dependent.
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ACKNOWLEDGMENTS
The authors thank Dr. Dan Wang, Dr. Yapeng Lu, Dr. Zhangji Dong and Dr. Xiaomei Wu who kindly provided suggestions to the study.
Funding
The study was supported by the National Natural Science Foundation of China (31500965, 31471141, 31671206), the Priority Academic Program Development of Jiangsu Higher Education Institution (PAPD) and Jiangsu Overseas Visiting Scholar Program for University Prominent Young and Middle-aged Teachers and Presidents.
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The study was approved by the Ethics Committee of the Human Research Ethics Committee of the Affiliated Hospital of Nantong University (2017-K036). Written informed consent was obtained from the patients for publication of this study.
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Abbreviations: NRF-1, nuclear respiratory factor 1; ChIP, chromatin immunoprecipitation.
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Wang, X.T., Cheng, K. & Zhu, L. Hypoxia Accelerate β-Actin Expression through Transcriptional Activation of ACTB by Nuclear Respiratory Factor-1. Mol Biol 55, 398–404 (2021). https://doi.org/10.1134/S0026893321020011
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DOI: https://doi.org/10.1134/S0026893321020011