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健康个体气道中与年龄相关的基因和 miRNA 表达变化。

Age-related gene and miRNA expression changes in airways of healthy individuals.

机构信息

University of Groningen, University Medical Center Groningen, Department of Pathology and Medical Biology, Groningen, The Netherlands.

University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD (GRIAC), Groningen, The Netherlands.

出版信息

Sci Rep. 2019 Mar 6;9(1):3765. doi: 10.1038/s41598-019-39873-0.

DOI:10.1038/s41598-019-39873-0
PMID:30842487
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6403379/
Abstract

Knowledge on age-related miRNA changes in healthy individuals and their interaction with mRNAs is lacking. We studied age-related mRNA and miRNA expression changes and their interactions in normal airways. RNA and small RNA sequencing was performed on bronchial biopsies of 86 healthy individuals (age: 18-73) to determine age-related expression changes. Per age-related miRNA we determined the enrichment of age-related predicted targets and their correlation. We identified 285 age-related genes and 27 age-related miRNAs. Pathway enrichment showed that genes higher expressed with age were involved in synapse-related processes. Genes lower expressed with age were involved in cell cycle regulation, the immune system and DNA damage/repair. MiR-146a-5p, miR-146b-5p and miR-142-5p were lower expressed with increasing age and we found a significant enrichment for predicted targets of these miRNAs among genes that were higher expressed with age. The expression levels of the enriched predicted targets RIMS2 and IGSF1 were negatively correlated with both miR-146a-5p and miR-146b-5p. RIMS2 was present in the enriched process, i.e. positive regulation of synaptic transmission. In conclusion, genes decreased with ageing are involved in several of the ageing hallmarks. Genes higher expressed with ageing were involved in synapse-related processes, of which RIMS2 is potentially regulated by two age-related miRNAs.

摘要

关于健康个体中与年龄相关的 miRNA 变化及其与 mRNAs 相互作用的知识尚不清楚。我们研究了正常气道中与年龄相关的 mRNA 和 miRNA 表达变化及其相互作用。对 86 名健康个体（年龄：18-73 岁）的支气管活检进行了 RNA 和小 RNA 测序，以确定与年龄相关的表达变化。对于每个与年龄相关的 miRNA，我们确定了与年龄相关的预测靶标及其相关性的富集。我们确定了 285 个与年龄相关的基因和 27 个与年龄相关的 miRNA。通路富集表明，随着年龄的增长而表达较高的基因与突触相关过程有关。随着年龄的增长而表达较低的基因与细胞周期调控、免疫系统和 DNA 损伤/修复有关。miR-146a-5p、miR-146b-5p 和 miR-142-5p 的表达随年龄的增长而降低，我们发现这些 miRNA 的预测靶标在与年龄相关的基因中显著富集。富含的预测靶标 RIMS2 和 IGSF1 的表达水平与 miR-146a-5p 和 miR-146b-5p 呈负相关。RIMS2 存在于富集的过程中，即突触传递的正调节。总之，随着年龄的增长而减少的基因与几种衰老标志有关。随着年龄的增长而表达较高的基因与突触相关过程有关，其中 RIMS2 可能受到两种与年龄相关的 miRNA 的调节。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c1b/6403379/3cf491c49748/41598_2019_39873_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c1b/6403379/750dbfe0c8d8/41598_2019_39873_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c1b/6403379/62b87ddbb278/41598_2019_39873_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c1b/6403379/22b991a8caf4/41598_2019_39873_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c1b/6403379/3cf491c49748/41598_2019_39873_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c1b/6403379/750dbfe0c8d8/41598_2019_39873_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c1b/6403379/62b87ddbb278/41598_2019_39873_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c1b/6403379/22b991a8caf4/41598_2019_39873_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c1b/6403379/3cf491c49748/41598_2019_39873_Fig4_HTML.jpg

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