Modulation of micrornas in pancreatic cancer by the dietary agent curcumin

Pancreatic tumourigenesis is a furtive disease characterised by its lack of palpable symptoms and the inconsistency in expression of its various diagnostic markers. The early detection of pancreatic cancer is therefore problematic, with most patients presenting with advanced disease resulting in limited treatment options. MicroRNAs post-transcriptionally regulate gene expression and their aberrant expression has been linked to disease progression in various cancers including pancreatic. In vitro studies have shown that by manipulating microRNA expression, it is possible to inhibit proliferation, suppress metastasis and induce drug sensitivity in pancreatic cancer cells. The phytochemical curcumin, which is under investigation in combination treatment trials for pancreatic cancer, is believed to alter microRNA expression. The work presented in this thesis aimed to identify novel, aberrantly expressed microRNAs which could potentially be used as diagnostic markers for pancreatic cancer, and to ascertain if curcumin could modulate their expression. Additionally, possible mechanisms by which curcumin may regulate the expression of key microRNAs in pancreatic cancer cells when compared to non-transformed cells were also examined. This thesis details the identification of differentially expressed microRNAs using microarray analysis. Cell viability and growth were assessed in order to determine a dose and a treatment time with the capacity to elicit a biological response in pancreatic cancer cell lines. Validation of changes observed in microRNA expression using the microarrays was carried out using RT-qPCR. The results demonstrated that, despite being unable to validate the differential expression of various microRNAs identified by microarray analysis, curcumin did appear to modulate the expression of a number of miRNAs known to be deregulated in pancreatic cancer.