How a mixture of microRNA-29a (miR-29a) and microRNA-144 (miR-144) cancer biomarkers interacts with a graphene quantum dot

Abstract

MicroRNAs (miRNAs) which are small non-coding RNAs have been reported to be potential cancer biomarker. However, it is difficult to extract such short RNA from a sample matrix. New effective strategies are required. Recently, graphene quantum dots (GQDs) have been used to detect nucleotides in many biosensor platforms, but their applications for miRNA extraction remain limited. GQD was reported to be able to collect short miRNA, but its performance to collect miRNAs with different structure remains unknown. Thus, in this work, the capability of GQD to interact with two different miRNAs is investigated. A mixture of hairpin-like miR-29a and circular miR-144 molecules are used as a representative of two miRNA morphologies. Two systems (a miRNA mixture, comprising 4 of miR-29a and 4 of miR-144, with (miR_GQD) and without GQD (miR)) were studied in comparison. MiRNAs in a mixture (miR) can aggregate, but no permanent miRNA assembly is captured. In contrast, the presence of GQD can rapidly and spontaneously activate the permanent miRNA/GQD clustering. This finding highlights the ability of GQD to be a miRNA collector. Interestingly, all GQD-bound miRNAs do not unfold. This allows the easy accessibility for probes. Also, nano-sized GQD seems to prefer hairpin miR-29a. The free 5’ terminus of miR-29a acts as the sticky end to adhere on GQD. This work highlights the importance of RNA secondary structure on GQD/miRNA aggregation capability. An insight obtained here will be useful for further design of miRNA isolation strategies.