Secreted microRNAs (miRNAs) from cells to blood maybe the novel class of signaling molecules mediating intercellular/interorgan communication. A research article, published this week in Molecular Cell, reports that miRNA can be secreted from one type of cells and delivered into recipient cells, decreases targeted gene expression, thus, regulates recipient cell function.
MiRNAs are a class of naturally occurring small non-coding RNAs that have been linked to biological possesses and diseases development. In the previous study, Chen-Yu Zhang and colleagues reported that expression profile of circulating miRNAs in human and other animals are the novel class of biomarkers for diagnosis of cancer and other diseases. As the consequent work, the same research team has investigated the source of circulating miRMAs. Chen-Yu Zhang and colleagues demonstrate that cell selectively packages miRNA into microvesicles when cell responses to different stimuli. The selective packaging is an essential point of specificity of cellular secretion of miRNAs. The research team also demonstrates that these secreted miRNAs can be delivered into target cells and can modulate the biological functions of these cells via repression of miRNA target gene expression.
"Since their discovery in C. elegans 15 years ago, miRNAs have been implicated in a wide array of cellular and developmental processes. To date, more than 500 miRNAs are predicted to be expressed in humans and nearly 30% of genes are predicted to be regulated by miRNAs. The present study extends our understanding of the role of miRNAs by illustrating that miRNAs can be secreted and delivered into target cells and that these exogenous miRNAs can alter the cellular functions of the recipient cells by modulating the expression of their target genes," said Chen-Yu Zhang. "From this point of view, secreted miRNAs represent a novel class of signaling molecules that play an important role in mediating cell-to-cell and organ-to-organ communication." Moreover, the secretion and targeting of miRNAs establishes a highly regulated complex network under various physiological and pathophysiological conditions.
"Compared to classic cellular communications mediated by hormone/cytokine–receptor and antigen–antibody interactions that generally occur only in certain types of cells, involve a single or few molecules, and affect target cells in a "one-way" fashion, secreted miRNA–based cell communication has the potential to function for every type of cell, to deliver many types of miRNAs with each miRNA targeting multiple genes, and to affect target cells in "two-way" or "multi-way" fashion. Investigating this secreted miRNA–mediated shift of cell communication from a "cable telephone" to "cell phone" fashion would help us to further understand the nature of biological signaling, discover novel mechanisms of disease and develop new therapeutic strategies," added by co-author Ke Zen.
The researchers include Yujing Zhang1,¶, Danqing Liu1,¶, Xi Chen1,¶, Jing Li1, Limin Li1, Zhen Bian1, Fei Sun2, Jiuwei Lu2, Yuan Yin1, Xing Cai1, Qi Sun1, Kehui Wang1, Yi Ba3, Qiang Wang4, Dongjin Wang4, Junwei Yang5, Pingsheng Liu2, Tao Xu2, Qiao Yan1, Junfeng Zhang1,*, Ke Zen1,*, and Chen-Yu Zhang1,* of 1Jiangsu Diabetes Center, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing, Jiangsu 210093, China; 2The Laboratory of Biological Electron Microscopy and Structural Biology Centre for Biological Imaging, Institute of Biophysics Chinese Academy of Sciences,15 Datun Road, Chaoyang District, Beijing 100101, China; 3Tianjin Medical University Cancer Institute and Hospital, Tianjin 300000, China; 4Department of Thoracic Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, China; 5Reseach Center of Nephrology, Nanjing Medical University; The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210000, China.
This work was supported by grants from the National Natural Science Foundation of China (no. 90813035, 30890044, 30570731), National Basic Research Program of China (973 Program) (no. 2006CB503908, 2006CB503909, 2004CB518603, 2003CB715905), the "111" Project, and the Natural Science Foundation of Jiangsu Province (no. BK2004082, BK2006714).
Zhang et al.: "Secreted monocytic miR-150 enhances targeted endothelial cell migration" Publishing in Molecular Cell, July 9th 2010.
Author contact
Chen-Yu Zhang (School of Life Sciences, Nanjing University, Nanjing, China)
Tel: +86 25 8368 6234; E-mail: cyzhang@nju.edu.cn
Journal
Molecular Cell