Pancreatic ductal
adenocarcinoma (PDAC) is extremely malignant and the therapeutic options available usually have little impact on survival. Great hope is placed on new therapeutic targets, including long noncoding RNAs (lncRNAs), and on the development of new drugs, based on e.g., broccoli-derived
sulforaphane, which meanwhile has shown promise in pilot studies in patients. We examined whether
sulforaphane interferes with
lncRNA signaling and analyzed five PDAC and two nonmalignant cell lines, patient tissues (
n = 30), and online patient data (n = 350). RT-qPCR, Western blotting, MTT, colony formation, transwell and wound healing assays; gene array analysis; bioinformatics; in situ hybridization; immunohistochemistry and
xenotransplantation were used.
Sulforaphane regulated the expression of all of five examined lncRNAs, but basal expression, biological function and inhibition of H19 were of highest significance. H19
siRNA prevented colony formation, migration, invasion and Smad2 phosphorylation. We identified 103 common
sulforaphane- and H19-related target genes and focused to the virus-induced
tumor promoter APOBEC3G. APOBEC3G
siRNA mimicked the previously observed H19 and
sulforaphane effects. In vivo,
sulforaphane- or H19 or APOBEC3G siRNAs led to significantly smaller
tumor xenografts with reduced expression of Ki67, APOBEC3G and phospho-Smad2. Together, we identified APOBEC3G as H19 target, and both are inhibited by
sulforaphane in prevention of PDAC progression.