MicroRNA noise reduction mechanism and accurate tumor cell recognition

Tsinghua News Network, August 26.
Recently, based on the research idea of ​​"digital-carbon-based fusion", Wang Xiaowo's research group from the Department of Automation of Tsinghua University revealed the gene expression noise reduction mechanism of microRNA and applied it to synthetic gene circuits Design, by guiding the construction of an artificial gene cell classifier, the precise identification of tumor cells has been achieved
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Since the beginning of this century, synthetic biology has achieved vigorous development as an emerging discipline, and has shown great application potential in the fields of medicine and health, metabolic engineering, and environmental protection
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Synthetic biologists get inspiration from electronic circuits.

As a biomolecule that is expressed in different cells, microRNA is often used as a marker to indicate cell type and cell state, and has been widely used in synthetic biology as a system input
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MicroRNAs are generally considered to suppress gene expression levels at the post-transcriptional level, thereby regulating many physiological and pathological processes; however, most microRNAs have very weak inhibitory ability to their target RNAs, and the biological functions of such microRNA-target RNA interaction relationships It has not been fully revealed yet

Analysis of microRNA regulation of "number-based-carbon-based fusion"

In the preliminary research, Wang Xiaowo's research group proposed the "number-based-carbon-based fusion" research idea, established a unified mathematical model of competitive regulation, and combined mathematical models and synthetic biology experiments to jointly reveal endogenous competition The quantitative influence of sex RNA on the regulatory ability of microRNA
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On this basis, the research team predicted that when gene expression levels are similar, competitive RNA with weaker interaction strength can play a role in buffering gene expression noise

Classification effect of artificial gene cell classifier

The above results reveal the importance of the microRNA-target RNA relationship with weak intracellular interaction in maintaining the stability of gene expression, and prove that the rational design of microRNA and its targets can control gene expression noise, thereby enhancing the synthetic gene circuit Performance
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This work shows that the complex phenomena caused by resource competition and gene expression noise must be fully considered in the design of synthetic gene circuits.

Related results were published in the Cell series journal "Characterizing microRNA-mediated modulation of gene expression noise and its effect on synthetic gene circuits" (Characterizing microRNA-mediated modulation of gene expression noise and its effect on synthetic gene circuits).
"Report" (Cell Reports)
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Professor Wang Xiaowo from the Department of Automation is the corresponding author of this article, Wei Lei, a postdoctoral fellow in the Department of Automation, and Li Shuilin, an undergraduate from the School of Life Sciences, are the co-first authors of this article.

Paper link:

https://