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Abstract

Small non-coding RNAs (sncRNAs) are short fragments of RNA (<200 nts) that regulate gene expression. There are several species including microRNAs (miRNAs), and PIWI-interacting RNAs (piRNAs), which function to regulate gene expression in cells. While they were initially disregarded as random fragments from degradation, improvements in RNA sequencing allowed for their high-throughput discovery. Since the early 2000s, the dysregulation of sncRNAs in diseases like cancer has been increasingly recognized. As cancer is one of the most prevalent and deadly diseases worldwide, finding alternative methods to improve early detection and treatment is of utmost importance. Therefore, this thesis explores the expression of tissue-specific sncRNAs and aims to characterize and expand the current sncRNA transcriptome. First, I analyzed small RNAseq data from publicly available thyroid and gastric cancer datasets to identify unannotated miRNAs, which were expressed in tumour and/or normal tissues. After manual filtering, I identified 170 novel miRNAs in gastric adenocarcinoma and 234 novel miRNAs in thyroid cancer. Following that, I used a prediction software to determine potential gene targets of novel miRNAs which were differentially expressed between non-malignant and tumour tissue. Furthermore, we determined that there is clinical significance of novel miRNAs in gastric adenocarcinoma Next, I characterized piRNAs in somatic non-malignant lung tissue and non-small cell lung cancer and compared their expression to those in fetal lung tissue. I identified a subset of 30 piRNAs in lung adenocarcinoma and 40 piRNAs in lung squamous cell carcinoma which were expressed in fetal and tumour tissue but not expressed in non-neoplastic lung tissue and were classified as oncofetal. Some of these were associated with overall survival and a signature of eight piRNAs identified in lung adenocarcinoma could combine to stratify high and low risk groups. The research presented in this thesis highlights the importance of non-coding changes in tumours. Dysregulated sncRNAs are predicted to target cancer-related pathways and are associated with overall survival. SncRNAs even display oncofetal expression, which represents a novel opportunity to discover potentially important regulators in development and tumorigenesis. All these combined warrants further investigation into their biological roles, prognostic implications, and therapeutic potential in cancer.