MicroRNAs (miRNAs) are crucial regulators in various pathological and physiological processes, and their misregulation is a hallmark of many diseases. In this study, we introduce an advanced DNA nanomachine using split-type molecular beacons (STMBs) for sensitive detection of miR-21, a key biomarker in cancer diagnostics. Utilizing an innovative STMB-mediated cascade strand displacement amplification (STMB-CSDA) technique, our approach offers a powerful means for the precise quantification of miRNAs, using miR-21 as a primary example. The system operates through target-induced linkage of STMBs, initiating a series of strand displacement amplifications resulting in exponential signal amplification. Coupled with the precision of T4 DNA ligase, this mechanism translates minimal miRNA presence into significant fluorescence signals, offering detection sensitivity as low as 5.96 pM and a dynamic range spanning five orders of magnitude. Characterized by its high specificity, which includes the ability to identify single-base mismatches, along with its user-friendly design, our method represents a significant leap forward in miRNA analysis and molecular diagnostics. Its successful application in examining total RNA from cancer cells and clinical serum samples demonstrates its immense potential as a groundbreaking tool for early cancer detection and gene expression studies, paving the way for the next generation of non-invasive diagnostics in personalized healthcare.

中文翻译：

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超灵敏 miRNA 检测：一种新型 DNA 纳米机器，利用分裂型分子信标介导的级联扩增进行癌症诊断


MicroRNA (miRNA) 是各种病理和生理过程中的重要调节因子，它们的失调是许多疾病的标志。在这项研究中，我们引入了一种先进的 DNA 纳米机器，使用分裂型分子信标 (STMB) 来灵敏检测 miR-21，这是癌症诊断中的关键生物标志物。我们的方法利用创新的 STMB 介导的级联链置换扩增 (STMB-CSDA) 技术，以 miR-21 作为主要示例，为 miRNA 的精确定量提供了强大的手段。该系统通过目标诱导的 STMB 连接进行操作，启动一系列链置换扩增，导致指数信号放大。与 T4 DNA 连接酶的精度相结合，该机制将最小的 miRNA 转化为显着的荧光信号，提供低至 5.96 pM 的检测灵敏度和跨越五个数量级的动态范围。我们的方法具有高特异性，包括识别单碱基错配的能力，以及用户友好的设计，代表了 miRNA 分析和分子诊断的重大飞跃。它在检查癌细胞和临床血清样本中的总 RNA 方面的成功应用表明了其作为早期癌症检测和基因表达研究的突破性工具的巨大潜力，为个性化医疗保健中的下一代非侵入性诊断铺平了道路。