Selective expression of tumor necrosis factor-related apoptosis-inducing ligand mediated by microRNA suppresses renal carcinoma growth.

Renal cell carcinoma (RCC) is the most common types among kidney cancers. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) strongly induces apoptosis in RCC. However, TRAIL therapy also leads to hepatotoxicity. To improve the biosafety, we inserted miRNA response elements (MREs) of miR-138, miR-199, and miR-122 into an adenoviral vector, Ad-TRAIL-3MREs, to restrict TRAIL expression within RCC cells. Luciferase assays showed that MREs can regulate the expression of exogenous gene in RCC cells. Ad-TRAIL-3MREs selectively expressed TRAIL and induce apoptosis in RCC cells, but not in normal cells. MTT assays revealed that Ad-TRAIL-3MREs reduced viability of RCC cells without cytotoxicity to normal cells. Ad-TRAIL-3MREs suppressed the growth of ACHN tumors and exerted no hepatotoxicity in vivo. Collectively, we generated a TRAIL-expressing adenoviral vector under the regulation of MREs. This miRNA-based gene therapy may be a promising strategy for RCC treatment.