Class�C1 decoy oligodeoxynucleotide inhibits profibrotic genes expression in rat hepatic stellate cells

Abstract

The aim of the present study was to investigate whether class c1 decoy oligodeoxynucleotides (odns) can inhibit the expression of pro-fibrotic genes associated with rat hepatic stellate cell (HSC) activation and hepatic fibrosis. luciferase reporter assays were performed to test the promoter activities of transforming growth factor (TGF)-β and its downstream target genes following transfection of decoy odns and plasmids into HSc-T6 cells, and western blot assays were performed to measure the protein expression of those genes following decoy ODN transfection. Class C1 decoy ODNs were confirmed to inhibit the promoter activity of TGF-β and its downstream target genes, such as type 1 collagen (coli)α1, tissue inhibitor of metalloproteinases (TiMP)1 and α-smooth muscle actin by Gaussia luciferase reporter assay, and to further downregulate the expression of TGF-β, SMad3, coliα1 and TiMP1 by western blotting in activated HSC-T6 cells. In conclusion, class C1 decoy ODNs inhibited pro-fibrotic gene expression in rat HSCS by downregulating TGF-β signaling.

Application of decoy oligodeoxynucleotides strategy for inhibition of cell growth and reduction of metastatic properties in nonresistant and erlotinib‐resistant SW480 cell line

“…Considering the benefits of TFD over the other STAT3 inhibitor strategies, such as small interfering RNA and monoclonal antibodies, specificity and efficiency in target binding, alongside the lower expenses of decoy ODNs synthesis, provides interest to the researchers (An et al, 2020; Gwon et al, 2020). Despite limitations in clinical development of ODNs in terms of stability and effective cell transfer, structural modifications are proposed to overcome these barriers and introduce ODNs as therapeutic candidates, especially in cases of drug resistance (Hecker & Wagner, 2017; Rao et al, 2020). These advantages have made the clinical application of STAT3 possible, for example, a report by Sen et al (2012b) who registered the first clinical trial of STAT3 decoy ODNs in head and neck tumors.…”