Understanding the oncogenic effects of C19MC on hepatocellular carcinoma through epigenetic manipulations.

Efendi, Emine (2021) Understanding the oncogenic effects of C19MC on hepatocellular carcinoma through epigenetic manipulations. Masters thesis, University of East Anglia.

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Abstract

Aberrant epigenetic alterations, such as DNA methylation, histone modification and miRNA-mediated processes, are associated with several types of cancer including hepatocellular carcinoma (HCC). HCC is the third leading cause of cancer-related fatalities worldwide. Despite the improvements in surgical and medical treatment HCC associated deaths are still showing an increase. Methylation defects at the chromosome 19 miRNA cluster (C19MC) have been shown to be a molecular alteration specific to liver cancers and is an attractive candidate for novel HCC therapies. Several C19MC miRNAs have been reported to be over-expressed in HCC and C19MC hypomethylation may account for this cancer-associated expression. This present study assesses the oncogenic effects of C19MC cluster in HCC using epigenetic manipulations. Using pharmaceutical and novel targeted epigenome editing tools demethylation was induced in HCC cell lines showing a normal hypermethylated state. Demethylation was shown to be sufficient to re-activate C19MC miRNAs throughout the cluster. Following overexpressing miR-512-3p through miRNA mimics, we showed that upregulation of miR-512-3p significantly promotes cell invasion. Since abnormal miRNA expression has been associated with metastatic spread of tumors, studying changes in miRNA expression could help to improve diagnosis and prognosis and provide molecular targets for new therapeutic strategies against HCC. Our study suggested that miR-512-3p can be a robust marker for HCC prognosis and diagnosis

Item Type: Thesis (Masters)
Faculty \ School: Faculty of Science > School of Biological Sciences
Depositing User: Chris White
Date Deposited: 25 Aug 2021 13:02
Last Modified: 25 Aug 2021 13:02
URI: https://ueaeprints.uea.ac.uk/id/eprint/81211
DOI:

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