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.
Department of Urology, China Japan Union Hospital of Jilin University, Changchun, 130033, China.
Zhuo
Z
Zhang
Haiyan
H
Zhang
Hongyan
H
Li
Xiaoliang
X
Chen
Meihan
M
Liu
Dayu
D
Liu
Yuanyuan
Y
Zhao
Xiangbo
X
Kong
D000256:Adenoviridae / Q000235:genetics; D001483:Base Sequence; D002292:Carcinoma, Renal Cell / Q000378:metabolism / Q000473:pathology*; D017931:DNA Primers; D005822:Genetic Vectors; D006801:Humans; D007680:Kidney Neoplasms / Q000378:metabolism / Q000473:pathology*; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology*; D016133:Polymerase Chain Reaction; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics / Q000502:physiology*
D017931:DNA Primers; D035683:MicroRNAs; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human