Sewer Alain, Zanetti Filippo, Iskandar Anita R, Guedj Emmanuel, Dulize Remi, Peric Dariusz, Bornand David, Mathis Carole, Martin Florian, Ivanov Nikolai V, Peitsch Manuel C, Hoeng Julia
PMI R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, CH-2000 Neuchâtel, Switzerland.
Toxicol Rep. 2020 Sep 12;7:1282-1295. doi: 10.1016/j.toxrep.2020.09.001. eCollection 2020.
The expression of some microRNAs (miRNA) is modulated in response to cigarette smoke (CS), which is a leading cause of major preventable diseases. However, whether miRNA expression is also modulated by the aerosol/extract from potentially reduced-risk products is not well studied. The present work is a meta-analysis of 12 studies in human organotypic epithelial cultures of the aerodigestive tract (buccal, gingival, bronchial, nasal, and small airway epithelia). These studies compared the effects of exposure to aerosols from electronic vapor (e-vapor) products and heated tobacco products, and to extracts from Swedish snus products (in the present work, will be referred to as reduced-risk products [RRPs]) on miRNA expression with the effects of exposure to CS or its total particulate matter fraction. This meta-analysis evaluated 12 datasets of a total of 736 detected miRNAs and 2775 exposed culture inserts. The t-distributed stochastic neighbor embedding method was used to find similarities across the diversity of miRNA responses characterized by tissue type, exposure type, and product concentration. The CS-induced changes in miRNA expression in gingival cultures were close to those in buccal cultures; similarly, the alterations in miRNA expression in small airway, bronchial, and nasal tissues resembled each other. A supervised clustering was performed to identify miRNAs exhibiting particular response patterns. The analysis identified a set of miRNAs whose expression was altered in specific tissues upon exposure to CS (, miR-125b-5p, miR-132-3p, miR-99a-5p, and 146a-5p). Finally, we investigated the impact of RRPs on miRNA expression in relation to that of CS by calculating the response ratio between the RRP- and CS-induced alterations at an individual miRNA level, showing reduced alterations in miRNA expression following RRP exposure relative to CS exposure (94 % relative reduction). No specific miRNA response pattern indicating exposure to aerosols from heated tobacco products and e-vapor products, or extracts from Swedish snus was identifiable.
一些微小RNA（miRNA）的表达会因应香烟烟雾（CS）而受到调节，香烟烟雾是主要可预防疾病的主要病因。然而，miRNA表达是否也会受到潜在风险降低产品的气溶胶/提取物的调节，目前尚未得到充分研究。本研究是对12项关于上消化道（颊、牙龈、支气管、鼻腔和小气道上皮）人体器官型上皮培养的研究进行的荟萃分析。这些研究比较了接触电子烟产品和加热烟草产品的气溶胶以及瑞典口含烟产品的提取物（在本研究中，将被称为风险降低产品[RRP]）对miRNA表达的影响与接触CS或其总颗粒物部分的影响。该荟萃分析评估了总共736个检测到的miRNA和2775个暴露培养皿的12个数据集。使用t分布随机邻域嵌入方法来发现以组织类型、暴露类型和产品浓度为特征的miRNA反应多样性之间的相似性。CS诱导的牙龈培养物中miRNA表达变化与颊部培养物中的变化相近；同样，小气道、支气管和鼻腔组织中miRNA表达的改变彼此相似。进行了监督聚类以识别表现出特定反应模式的miRNA。分析确定了一组miRNA，其表达在接触CS后在特定组织中发生改变（，miR-125b-5p、miR-132-3p、miR-99a-5p和146a-5p）。最后，我们通过计算个体miRNA水平上RRP和CS诱导的改变之间的反应比，研究了RRP对miRNA表达的影响与CS的关系，结果显示与CS暴露相比，RRP暴露后miRNA表达的改变减少（相对减少94%）。未发现表明接触加热烟草产品和气溶胶产品或瑞典口含烟提取物的特定miRNA反应模式。
