Tracing cellular interaction of circRNA-miRNA axis with Cu metal-organic framework supported DNA cascade assembly

Circular RNAs (circRNAs) can act as molecular sponges of microRNA (miRNA) to form circRNA-miRNA axis, which regulates the expressions of downstream proteins. Although the mechanism has been widely reported in various bioprocesses, there is still a lack of reliable and facile way to intuitively monitor and locate the interaction between circRNA and miRNA inside living cells. In this study, multiple DNA probes are designed and loaded onto two-dimensional Cu metal-organic framework (2D Cu-MOF) nanosheets for one-step analysis of circRNA-miRNA axis. The nanosheets serve as not only powerful fluorescence quenchers but also excellent nanocarriers of abundant DNA probes for further assembly. The Probes@Cu-MOF complex can be applied to track the circRNA-miRNA axis in living cells with high sensitivity and co-localization analysis. This platform combines the transmembrane advantage of nanosheets and the signal amplification ability of localized DNA cascade assembly, so it holds great potential for understanding the biological functions of circRNA-miRNAs in cancer pathogenesis and for therapeutic applications.