UBC Theses and Dissertations

UBC Theses Logo

UBC Theses and Dissertations

Deregulation of small non-coding RNAs in response to environmental carcinogens and during human development Martinez, Victor D.


Asbestos and arsenic are human carcinogens. Exposure to asbestos, a group of mineral fibers used in construction materials and daily-use products, has been directly associated with the development of mesothelioma and lung cancer (LC). Arsenic can contaminate drinking water, resulting in >200 million individuals worldwide at increased risk of developing LC, amongst other diseases. The molecular damage induced by these carcinogens accumulates during our lifetime, even before birth; however, early damage is masked by the time of disease diagnosis. Thus, there is a need for markers that inform about tissue-specific etiology and increased risk of developing environmentally-induced cancers. Small non-coding RNAs (sncRNAs) are key regulators of gene expression. Their potential as biomarkers have been studied in a variety of malignancies, including mesothelioma and LC. The use of next-generation sequencing (NGS) has enabled the discovery of novel sncRNAs with an enhanced tissue-specificity, which makes them candidates for tissue-specific markers. Similarly, the sncRNA expression pattern in organs that determine human development, such as the placenta, is relevant as the effects of environmental exposures can occur before birth and are determined by the unique features of the placenta genome and epigenome. Here, we aim to define if human tissues express specific sets of previously-uncharacterized sncRNAs in response to environmental carcinogens and during fetal development. The two underlying hypotheses for this work are: i) mesothelioma tumours express previously-unidentified sncRNA in a tissue-specific manner, which can be exploited as tissue-of-origin markers, and ii) sncRNA expressed in the human placenta have a specific expression pattern, different from other organs. To test these hypotheses, we have analyzed sncRNA sequencing data derived from mesothelioma and lung tumours as well as from human placenta samples to perform an unbiased analysis of its sncRNA transcriptome and to define unique features. Finally, we also investigated the temporal changes in sncRNA expression in lung cell models induced by chronic exposure to arsenic, as future directions for developing markers to identify arsenic-induced molecular damage. Collectively, the results from this work will contribute to understanding the molecular mechanisms mediated by sncRNAs during environmentally-induced molecular damage, as well as their role in the human placenta.

Item Citations and Data


Attribution-NonCommercial-NoDerivatives 4.0 International