文章：

基于miR-15/107共有序列的合成microRNA模拟物的治疗潜力

Therapeutic potential of synthetic microRNA mimics based on the miR-15/107 consensus sequence 

原文发布日期：2025-03-22 

英文摘要：

MicroRNA expression is frequently suppressed in cancer, and previously we demonstrated coordinate downregulation of multiple related microRNAs of the miR-15/107 group in malignant pleural mesothelioma (PM). From an alignment of the miR-15 family and the related miR-103/107, we derived a consensus sequence and used this to generate synthetic mimics. The synthetic mimics displayed tumour suppressor activity in PM cells in vitro, which was greater than that of a mimic based on the native miR-16 sequence. These mimics were also growth inhibitory in cells from non-small cell lung (NSCLC), prostate, breast and colorectal cancer, and sensitised all cell lines to the chemotherapeutic drug gemcitabine. The increased activity corresponded to enhanced inhibition of the expression of target genes and was associated with an increase in predicted binding to target sites, and proteomic analysis revealed a strong effect on proteins involved in RNA and DNA processes. Applying the novel consensus mimics to xenograft models of PM and NSCLC in vivo using EGFR-targeted nanocells loaded with mimic led to tumour growth inhibition. These results suggest that mimics based on the consensus sequence of the miR-15/107 group have therapeutic potential in a range of cancer types. 

摘要翻译：

MicroRNA在癌症中的表达常受到抑制，此前我们已证明恶性胸膜间皮瘤（PM）中miR-15/107家族多个相关microRNA存在协同下调现象。通过比对miR-15家族及相关的miR-103/107序列，我们推导出共有序列并据此合成模拟物。该合成模拟物在体外PM细胞中展现出比天然miR-16序列模拟物更强的肿瘤抑制活性。这些模拟物对非小细胞肺癌（NSCLC）、前列腺癌、乳腺癌和结直肠癌细胞同样具有生长抑制作用，并使所有细胞系对化疗药物吉西他滨的敏感性增强。活性增强对应着对靶基因表达的抑制效果提升，且与预测靶点结合力的增加相关——蛋白质组学分析显示其对参与RNA和DNA过程的蛋白质产生显著影响。通过EGFR靶向纳米载体装载该新型共有序列模拟物应用于PM和NSCLC异种移植模型后，实现了体内肿瘤生长抑制。这些结果表明基于miR-15/107家族共有序列的模拟物具有治疗多种癌症类型的潜力。

原文链接：

Therapeutic potential of synthetic microRNA mimics based on the miR-15/107 consensus sequence