Study of the miR-17-92 network and potential miRNA-telomere associations in the ENVIRONAGE birth cohort

Abstract

Already early in life, people are exposed to environmental hazards, transported via the placenta to the foetus. In utero air pollution exposure can affect in ageing and cancer risk later in life. Epigenetic mechanisms, like miRNAs, are known to have a role in ageing, via telomere controlling, and potentially function in diseases induced by air pollution exposure. Telomere length (TL) at birth has already been associated with lifespan in zebra-finches as it determines the capacity of the cell to cope with inflammatory or oxidative processes throughout lifetime. Therefore, TL is associated with age-related diseases, like cancer. Therefore, it is hypothesised that placental candidate miRNAs are differentially expressed in association with TL at birth. Meanwhile, the oncogenic miR-17/92 cluster was shown to be related to prenatal air pollution exposure in cord blood. The cluster is involved in normal development and carcinogenesis by targeting genes in important biological processes, including cell proliferation, cell death and even hypoxia. It is hypothesised that the network around the oncogenic cluster is differentially expressed in association with prenatal air pollution exposure. Here, we investigate potential alterations (1) in the expression of the network, including regulators and targets of the cluster, in association with prenatal air pollution exposure and (2) in the miRNA expression of all known human miRNAs in the placenta in association with telomere length at birth.