A Versatile Electrochemical Biosensor for the Detection of Circulating MicroRNA toward Non‐Small Cell Lung Cancer Diagnosis

Abstract

Circulating microRNAs (miRNAs) can be used as noninvasive biomarkers and are also found circulating in body fluids such as blood. Dysregulated miRNA expression is associated with many diseases, including non‐small cell lung cancer (NSCLC), and the miRNA assay is helpful in cancer diagnosis, prognosis, and monitoring. In this work, a versatile electrochemical biosensing system is developed for miRNA detection by DNAzyme‐cleavage cycling amplification and hybridization chain reaction (HCR) amplification. With cleavage by Mn2+ targeted DNAzyme, DNA‐walker can move along the predesigned DNA tracks and contribute to the transduction and enhancement of signals. For the electrochemical process, the formation of multiple G‐quadruplex‐incorporated long double‐stranded DNA (dsDNA/G‐quadruplex) structures is triggered through HCR amplification. The introduction of G‐quadruplex allows sensitive measurement of miRNA down to 5.68 fM with good specificity. Furthermore, by profiling miRNA in the NSCLC cohort, this designed strategy shows high efficiency (area under the curve (AUC) of 0.879 using receiver operating characteristic (ROC) analysis) with the sensitivity of 80.0% for NSCLC early diagnosis (stage I). For the discrimination of NSCLC and benign disease, the assay displays an AUC of 0.907, superior to six clinically‐acceptable protein tumor markers. Therefore, this platform holds promise in clinical application toward NSCLC diagnosis and prognosis.

An enzyme-powered microRNA discriminator for the subtype-specific diagnosis of breast cancer

“…Table S1 † shows the comparison of the method developed in this study and the methods currently available for the quantication of miRNA. [41][42][43][44][45][46] The method developed in this study showed an improved sensitivity with a relatively wider linear range and a lower detection limit compared to the existing methods.…”

Simulation‐Assisted Localized DNA Logical Circuits for Cancer Biomarkers Detection and Imaging

“…For example, irregular expression of miRNAs and APE1 was detected in some normal cells. [27,28] As shown in Figure 1A, ATP bound its aptamer to release the blocked strand (module A), miR-141 opened the hairpin structure strand-specific endonuclease, only the activated modules A and M hybridized with high stability would LDC release signals. The ssDNA flexibility of the two modules might have a significant impact on the hybridization reaction, which in turn affected the signal output and sensitivity of LDC.…”

Emerging Roles of miRNA, lncRNA, circRNA, and Their Cross-Talk in Pituitary Adenoma

“…The abundance of DE ncRNAs in PA has been widely reported. Investigating the roles of ncRNAs is helpful for understanding the occurrence and development of PA, and some ncRNAs can be used as biomarkers for the detection of PA [ 1 , 18 , 43 , 127 ], while other ncRNAs can contribute to the diagnosis of PA [ 52 , 85 , 90 , 112 ], distinguish the disease subtypes [ 24 , 25 , 34 , 93 ], and predict tumor invasion and progression [ 20 , 26 , 35 , 85 , 95 , 110 , 111 , 123 ]; the remaining ncRNAs may be implicated in the pathogenesis of PA [ 116 , 117 , 120 , 122 ]. In addition, the regulatory networks of lncRNA/circRNA and miRNA provide promising biomarkers for the noninvasive diagnosis and molecular therapy of PA, and exosome-derived ncRNAs bring a tremendous infusion of hope to the improvement of the disease diagnosis and future potential therapeutic targets for treatments.…”

“…Among the abundant DE ncRNAs, miRNAs are the most widely studied. We discuss the role of miRNAs in different PA subtypes in tissues, biofluids, and cell-free environments [ 17 , 18 , 19 , 20 , 37 ]. miRNAs inhibit the expression of target genes at the post-transcriptional level by pairing with the 3′-UTR of mRNA ( Figure 1 ); thus, miRNAs are involved in various pathological and physiological processes by playing a negative role in cell proliferation, differentiation, metabolism, and apoptosis.…”