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Title: Investigation of the role of eukaryotic initiation factor 3f (eIF3f) and heterogeneous nuclear ribonucleoprotein K (hnRNP K) in stress induced RNA disruption in melanoma cells
Authors: Lizzi, Michayla
Keywords: Malignant melanoma;chemotherapy;RNA disruption;eukaryotic initiation factor 3f;heterogeneous nuclear ribonucleoprotein K
Issue Date: 30-Jul-2021
Abstract: The incidence of skin cancer has been on the rise over the last few decades. While it only represents a small percentage of skin cancers, melanoma is the deadliest skin malignancy. Malignant melanoma is very aggressive and displays both primary and acquired resistance to most therapies. A recent clinical trial has demonstrated that high tumour ribosomal RNA (rRNA) degradation during neoadjuvant chemotherapy can predict complete tumour destruction and improved survival for breast cancer patients. This phenomenon of RNA degradation in response to chemotherapy has been termed RNA disruption, and has been shown to occur in various cancer cell lines, but never in melanoma cells. While the molecular mechanisms involved in RNA disruption remain unclear, studies conducted by other groups have provided evidence that eukaryotic initiation factor 3f (eIF3f) and heterogeneous nuclear ribonucleoprotein K (hnRNP K) may play a role. Under stress eIF3f has been shown to associate with hnRNP K, and it has been proposed that this results in the displacement of hnRNP K from rRNA, allowing it to be degraded by as of yet unidentified ribonucleases. We propose that this may be an underlying mechanism in chemotherapy induced RNA disruption. In this study, we provide the first evidence that chemotherapy and stress-induced RNA disruption can occur in malignant melanoma cells in vitro. We further demonstrate that chemical stressors inducing RNA disruption also promote the loss of eIF3f and hnRNP K expression in melanoma cells, and that similar to RNA disruption, this loss of expression is both dose- and time-dependent. However, our studies could not confirm prior studies that eIF3f binding to hnRNP K is increased in cells exposed to chemical stressors. Nevertheless, the dramatic reduction in cellular levels of hnRNP K (a ribosome associated protein) might facilitate rRNA degradation, by permitting greater ribonuclease binding to rRNA
Appears in Collections:Biology - Master's Theses

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