Naomi Walsh
National Institute for Cellular Biotechnology, DCU, Ireland
Title: Genomic profiling and functional analysis of miRNA: mRNA interactions involved in invasive progression of pancreatic cancer
Biography
Biography: Naomi Walsh
Abstract
Pancreatic cancer is a devastating disease. The lethality of pancreatic cancer is related to its rapid growth and tendency to invade adjacent organs and metastasise at an early stage. Identification of targets which play a role in the highly invasive phenotype of pancreatic cancer may help to better understand the biological behaviour and the rapid progression of this cancer. A systematic evaluation of miRNA and mRNA expression profiling was performed in highly invasive and non-invasive sub-clones derived from the MiaPaCa-2 cell line. Differential expression between the highly invasive and non-invasive clones revealed 522 genes and 12 miRNAs altered (p<0.05; fold change > 2). The integrated analysis of miRNA:mRNA found significant anti-correlation with 11 genes co-regulated by eight miRs. Validation of the miRNA:mRNA interactions was performed in seven pancreatic cancer cell lines and corresponded with invasive capabilities. Furthermore, expression of 4 miRs (mir-9, mir-135b, mir-148a and let-7c) was independently established in 20 pancreatic cancer and adjacent normal tissue specimens. Functional miR-gene targeting was validated in primary cell lines (n=4) derived from pancreatic tissue and established pancreatic cancer cell lines. Let-7c was found to be down-regulated in highly invasive cell lines and lowly expressed in pancreatic tumour tissue. Let-7c negatively regulates SOX13 expression. SOX13 is a direct target of SHH signalling and RNAi knockdown of SOX13 reduced proliferation and invasion of pancreatic cancer cells. The identification of key miRNA:mRNA gene interactions and networks provide potential diagnostic and therapeutic strategies for better treatment options for pancreatic cancer patients.
