In this study , scientists from Professor Jong Soon Kang’s group in KRIBB and Ractigen collaborated on utilizing small activating RNAs (saRNAs) to upregulate an important tumor suppressor gene Von Hippel-Lindau (VHL) in renal cell carcinoma (RCC). From screening 4 saRNAs targeting the promoter of VHL, they identified an saRNA (dsVHL-821) which could readily activate VHL mRNA and protein expression, resulting in inhibited cell growth and apoptotic cell death. Mechanistically, they found that dsVHL-821 induced apoptosis by increasing p53 and decreasing Bcl-xL expression. In addition, targeting the promoter of VHL by dsVHL-821 led to enrichment of Ago2 and RNA polymerase II at the dsVHL-821 target site, accompanied by an increase in dimethylation of histone 3 at lysine 4 (H3K4me2) and acetylation of histone 4 (H4ac) and a decrease in dimethylation of histone 3 at lysine 9 (H3K9me2) and lysine 27 (H3K27me2). This study demonstrates that targeted activation of tumor suppressor gene VHL by saRNA may be explored as a novel treatment of RCC. Developing saRNA-based therapeutics for RCC could further expand Ractigen’s R&D pipeline.
1. Kang MR, Park KH, Lee CW, Lee MY, Han SB, Li LC, Kang JS. Small activating RNA induced expression of VHL gene in renal cell carcinoma. Int J Biochem Cell Biol. 2018 Feb: S1357-2725(18)30030-X.