Date of Award
In recent studies small nucleolar RNAs (snoRNA) have been shown to be processed into smaller microRNA-like fragments known as sno-derived RNA (sdRNA). We recently identified 9 snoRNAs that contribute to prostate malignancy using The Cancer Genome Atlas (TCGA) patient prostate tumor next-generation sequencing datasets. These snoRNA were found to be processed into sdRNAs, heavily misexpressed in prostate cancer cell types 8140 and 8550, and shown to function by binding Ago proteins in order to impact mRNA translation. SdRNA-19b and sdRNA-24 in particular stood out as having significant differential expression in prostate cancer vs. control tissue. Interestingly, the targets for sdRNA-19b and sdRNA-24 were then predicted to be well known tumor suppressors and oncogenes. SdRNA-19b aligned with STAT5b, CDK6 and CD44 while sdRNA-24 aligned with were predicted to be RHOH, Timp3 and AR, all of which were confirmed through the use of luciferase assays. Additionally, our phenotypic assays show that over-expressions of sdRNA-19b and sdRNA-24 lead to increased cell proliferation and over expressions of sdRNA-19b lead to increased cell migration rates, indicating a direct impact on sdRNA levels to the proliferative and migratory ability of prostate cancer cells. Current results also strongly indicate that when sdRNA-19b and sdRNA-24 are inhibited they are significantly less likely to survive the presence of chemotherapeutic agents, providing a new potential target for effective chemotherapy treatment. In summary, our results indicate that sdRNA-19b and sdRNA-24 actively contribute to the malignant phenotype of prostate cancer through miRNA-like regulation.
Barchie, Addison A., "The functionally relevant role of sdRNA-19b and sdRNA-24 in prostate cancer" (2021). Undergraduate Theses . 1.