Long non-coding RNAs in liver cancer chemoresistance.

Long non-coding RNAs (lncRNAs) have gained massive attention in recent years as a potentially new and crucial layer of gene regulation. Recently, researchers have started to explore the implications of lncRNAs alteration in hepatic pathophysiology. LncRNAs have been shown to play a major role in hepatocellular carcinoma (HCC). However, their implication in HCC chemoresistance has not been investigated. For this type of cancer, with increasing incidence and a high mortality rates, it is crucial to identify new therapeutic targets and biomarkers to predict response to therapy. LncRNAs may present a promising new resource.

We have established liver cancer cell lines resistant to compounds that are currently used in the clinic in the form of systemic chemotherapy for liver cancer patients. Expression arrays were employed to profile for lncRNAs along with the whole transcriptome of protein-coding genes. We have identi¬fied lncRNAs that are differentially expressed between the chemoresistant and the parental cell lines.

Through expression profiling studies in healthy and diseased tissues, the study aim to correlate deregulated lncRNAs with clinicopathological parameters. Importantly, correlation analysis will be performed in order to associate the expression pattern of specific lncRNAs with signatures of coding transcripts. The expression of the top two deregulated lncRNAs will be manipulated in order to study their functional properties in vitro. Subsequent molecular biology approaches will be employed to identify the interactome of lncRNAs. Upon sequence and functional conservation analyses, we will proceed to genetically target the two lncRNAs in mice and study their role in vivo. Finally, we aim to develop sequence specific oligonucleotides for the disruption of lncRNA-protein interactions. By applying in vitro and in vivo approaches we intent to experimentally test the efficacy of these oligonucleotides on liver cancer growth and aggressiveness. Overall, this project will shed light on the multifactorial process of drug resistance and provide novel targets for the treatment of liver cancer.

UK 1stClass / 2.1 Bachelor’s degree (or UK equivalent according to NARIC) and/or UK Master’s degree with a minimum of a merit/commendation (or UK equivalent according to NARIC) in Cell Biology, Biochemistry, Biology, Biological Chemistry, Pharmacology, Biomedical Sciences or a related discipline.