Pancreas‐specific tumor suppressor gene SEL1L is downregulated at both the mRNA and protein levels in a significant proportion of human pancreatic ductal adenocarcinoma (PDAC) cases. We sought to use statistical methods to determine if one or more aberrantly upregulated microRNAs (miRNA) are responsible for the repression of SEL1L, which would help elucidate the role of specific miRNAs in PDAC.
Based on published microRNAs microarray data and miRNA targets prediction resource, we initially identified seven miRNAs for our study which were reported to be upregulated in PDAC and potentially target SEL1L. Using real‐time PCR, we quantitatively assessed the expression levels of SEL1L mRNA and these miRNAs in 42 pairs of PDAC samples and matched normal adjacent tissues. Fisher's Exact Test and Kruskal‐Wallis Test were applied to evaluate the correlation between SEL1L and the miRNAs.
Our results showed that the expression of SEL1L mRNA inversely correlates with the expression of 3 miRNAs (P < 0.0001, P < 0.0001 and P = 0.002, respectively). As the number of these overexpressed miRNAs increase from 0 to 3, we observed progressively increasing downregulation of SEL1L (P − trend = 0.001).
Our findings suggest that the 3 miRNAs work cooperatively to repress SEL1L mRNA expression. These specific miRNAs may serve as useful biomarkers for PDAC.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):B52.