<p> Advances in next-generation sequencing and algorithm design have revealed the evolutionarily conserved expression of large numbers of circular RNAs (circRNAs) that are endogenous to eukaryotic cells, many being abundant and in some cases the exclusive output of a given gene. CircRNAs are produced when the pre-mRNA splicing machinery “backsplices” to join a 3’ downstream splice donor to a 5’ upstream splice acceptor. Their circular nature gives them superior resistance to exonucleases and extended half-lives when compared to linear RNAs. CircRNAs are produced in a regulated manner to carry out specific cellular functions, as supported by the identification of alternative splicing factors required for circularization. A generalized biological function for circRNAs has not been unequivocally identified. Aberrantly expressed circRNAs may contribute to tumorigenesis, maintenance or progression of cancer cells. In particular, altered circRNA can contribute to important aspects of melanoma biology, and even harbor prognostic and/or therapeutic value. This work is the first comprehensive, unbiased identification and characterization of circRNAs in melanoma, focusing particularly on circARID1A, a gained circRNA when comparing melanoma to non-transformed melanocytes. Silencing of either linear (protein coding) or circular ARID1A in melanoma cells results in impaired proliferation and distinct transcriptional outputs. SERBP1 was identified as an interacting partner of circARID1A, and as a potential mediator of its function. These studies shed light on the roles of circRNAs in cancer and their mechanisms of action, setting the path for future work on these RNA species in other malignancies.</p><p>
| Identifer | oai:union.ndltd.org:PROQUEST/oai:pqdtoai.proquest.com:10846959 |
| Date | 17 November 2018 |
| Creators | Ulloa Morales, Alejandro Jose |
| Publisher | New York University |
| Source Sets | ProQuest.com |
| Language | English |
| Detected Language | English |
| Type | thesis |
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