An “On-Off” self-powered biosensor via GOD activated signal transduction for ultrasensitive detection of multiple biomarkers

MicroRNA exhibits differential expression levels in cancer and can affect cellular transformation, carcinogenesis and metastasis. Although fluorescence techniques using dye molecule labels have been studied, label-free molecular-level quantification of miRNA is extremely challenging. We developed a surface plasmon resonance sensor based on two-dimensional nanomaterial of antimonene for the specific label-free detection of clinically relevant biomarkers such as miRNA-21 and miRNA-155. First-principles energetic calculations reveal that antimonene has substantially stronger interaction with ssDNA than the graphene that has been previously used in DNA molecule sensing, due to thanking for more delocalized 5s/5p orbitals in antimonene. The detection limit can reach 10 aM, which is 2.3–10,000 times higher than those of existing miRNA sensors. The combination of not-attempted-before exotic sensing material and SPR architecture represents an approach to unlocking the ultrasensitive detection of miRNA and DNA and provides a promising avenue for the early diagnosis, staging, and monitoring of cancer.

A major obstacle to improving prognoses in ovarian cancer is the lack of effective screening methods for early detection. Circulating microRNAs (miRNAs) have been recognized as promising biomarkers that could lead to clinical applications. Here, to develop an optimal detection method, we use microarrays to obtain comprehensive miRNA profiles from 4046 serum samples, including 428 patients with ovarian tumors. A diagnostic model based on expression levels of ten miRNAs is constructed in the discovery set. Validation in an independent cohort reveals that the model is very accurate (sensitivity, 0.99; specificity, 1.00), and the diagnostic accuracy is maintained even in early-stage ovarian cancers. Furthermore, we construct two additional models, each using 9–10 serum miRNAs, aimed at discriminating ovarian cancers from the other types of solid tumors or benign ovarian tumors. Our findings provide robust evidence that the serum miRNA profile represents a promising diagnostic biomarker for ovarian cancer.

MicroRNA (miRNA) biogenesis initiates co-transcriptionally, but how the Microprocessor machinery pinpoints the locations of short precursor miRNA sequences within long flanking regions of the transcript is not known. Here we show that miRNA biogenesis depends on DNA methylation. When the regions flanking the miRNA coding sequence are highly methylated, the miRNAs are more highly expressed, have greater sequence conservation, and are more likely to drive cancer-related phenotypes than miRNAs encoded by unmethylated loci. We show that the removal of DNA methylation from miRNA loci leads to their downregulation. Further, we found that MeCP2 binding to methylated miRNA loci halts RNA polymerase II elongation, leading to enhanced processing of the primary miRNA by Drosha. Taken together, our data reveal that DNA methylation directly affects miRNA biogenesis.