Intercellular communication has been transformed by the discovery of extracellular vesicles (EVs) and their cargo, including microRNAs (miRNAs), which play crucial roles in intercellular signaling. These EVs were previously disregarded as cellular debris but are now recognized as vital mediators of biological information transfer between cells. Furthermore, they respond not only to internal stimuli but also to environmental and lifestyle factors. Identifying EV-borne oncomiRs, a subset of miRNAs implicated in cancer development, could revolutionize our understanding of how environmental and lifestyle exposures contribute to oncogenesis. To investigate this, we studied the plasma levels of EV-borne oncomiRs in a population of 673 women and 238 men with a body mass index > 25 kg/m2(SPHERE population). The top fifty oncomiRs associated with the three most common cancers in women (breast, colorectal, and lung carcinomas) and men (lung, prostate, and colorectal carcinomas) were selected from the OncomiR database. Only oncomiRs expressed in more than 20% of the population were considered for statistical analysis. Using a Multivariate Adaptive Regression Splines (MARS) model, we explored the interactions between environmental/lifestyle exposures and EV oncomiRs to develop optimized predictor combinations for each EV oncomiR. This innovative approach allowed us to better understand miRNA regulation in response to multiple environmental and lifestyle influences. By uncovering non-linear relationships among variables, we gained valuable insights into the complexity of miRNA regulatory networks. Ultimately, this research paves the way for comprehensive exposome studies in the future.
细胞外囊泡及其携带物（包括在细胞间信号传导中起关键作用的微小核糖核酸）的发现，彻底改变了人们对细胞间通讯的认知。这些囊泡曾被视为细胞碎片而被忽视，如今却被确认为细胞间生物信息传递的重要媒介。值得注意的是，它们不仅响应内部刺激，还会受到环境与生活方式因素的影响。鉴定囊泡携带的致癌微小核糖核酸（一类参与癌症发展的微小核糖核酸亚型），可能从根本上改变我们对环境及生活方式暴露如何导致肿瘤发生的理解。为此，我们研究了673名女性和238名体重指数＞25 kg/m²男性（SPHERE人群）血浆中囊泡携带的致癌微小核糖核酸水平。我们从OncomiR数据库中筛选出与女性（乳腺癌、结直肠癌、肺癌）和男性（肺癌、前列腺癌、结直肠癌）三大最常见癌症相关的50种主要致癌微小核糖核酸，仅对在超过20%人群中表达的致癌微小核糖核酸进行统计分析。通过多元自适应回归样条模型，我们探究了环境/生活方式暴露与囊泡致癌微小核糖核酸之间的相互作用，为每种囊泡致癌微小核糖核酸构建了优化的预测因子组合。这种创新方法使我们能更好地理解微小核糖核酸在多重环境和生活方式影响下的调控机制。通过揭示变量间的非线性关系，我们获得了对微小核糖核酸调控网络复杂性的重要认识。这项研究最终为未来开展全面的暴露组学研究奠定了重要基础。
肿瘤(癌症)患者之家