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Putative tumor suppressor gene SEL1L was downregulated by aberrantly upregulated
hsa-mir-155 in human pancreatic ductal adenocarcinoma
#MMPMID23661430
Liu Q
; Chen J
; Wang J
; Amos C
; Killary AM
; Sen S
; Wei C
; Frazier ML
Mol Carcinog
2014[Sep]; 53
(9
): 711-21
PMID23661430
show ga
Sel-1-like (SEL1L) is a putative tumor suppressor gene that is significantly
downregulated in human pancreatic ductal adenocarcinoma (PDA). The mechanism of
the downregulation is unclear. Here, we investigated whether aberrantly
upregulated microRNAs (miRNAs) repressed the expression of SEL1L. From reported
miRNA microarray studies on PDA and predicted miRNA targets, we identified seven
aberrantly upregulated miRNAs that potentially target SEL1L. We assessed the
expression levels of SEL1L mRNA and the seven miRNAs in human PDA tumors and
normal adjacent tissues using real-time quantitative polymerase chain reaction.
Then statistical methods were applied to evaluate the association between SEL1L
mRNA and the miRNAs. Furthermore, the interaction was explored by functional
analysis, including luciferase assay and transient miRNA overexpression. SEL1L
mRNA expression levels were found to correlate inversely with the expression of
hsa-mir-143, hsa-mir-155, and hsa-mir-223 (P?0.0001, P?0.0001, and P?=?0.002,
respectively). As the number of these overexpressed miRNAs increased, SEL1L mRNA
expression progressively decreased (Ptrend ?=?0.001). Functional analysis
revealed that hsa-mir-155 acted as a suppressor of SEL1L in PDA cell lines. Our
study combined statistical analysis with biological approaches to determine the
relationships between several miRNAs and the SEL1L gene. The finding that the
expression of the putative tumor suppressor SEL1L is repressed by upregulation of
hsa-mir-155 helps to elucidate the mechanism for SEL1L downregulation in some
human PDA cases. Our results suggest a role for specific miRNAs in the
pathogenesis of PDA and indicate that miRNAs have potential as therapeutic
targets for PDA.