Abstract 4387: Up-regulation of VHL by miR-1273C inhibits renal cell carcinoma

Abstract

Abstract VHL (Von Hippel-Lindau) is a known tumor suppressor that binds to hypoxia inducible factor (HIF) and induces ubiquitin-mediated degradation. VHL is also involved in the regulation of tumor angigoenesis, cell cycle regulation, and apoptosis. Recent studies have reported that double strand RNA complementary to target promoter sequence can induce gene expression in several cancer cells and this is called small activating RNA (saRNA). By scanning gene promoters in silico for sequences complementary to known miRNAs, we identified 32 putative miRNAs target site in the promoter of VHL. Experimental validation identified two miRNAs (miR-1273C and miR-4512) that induce VHL expression in 769-P renal cancer cells. Another dsRNA molecule (dsVHL-101) complementary to the putative miR-1273C target site also induced VHL expression. Functional studies revealed that transfection of miR-1273C and dsVHL-101 inhibited cell proliferation and induced apoptosis in dose dependent manner. Furthermore, knockdown experiments confirmed that induction of VHL and apoptosis by miR-1273C and dsVHL-101 required the miRNA maturation protein Ago2 and nuclear transport protein TNRC6A. This study suggests that miRNAs play an inhibiting role in the progression of cancer cells by VHL gene expression, which may be a potential therapeutic approach in the future. Citation Format: Chang Woo Lee, Moo Rim Kang, Jieun Yun, Soo Jin Oh, Jong Soon Kang. Up-regulation of VHL by miR-1273C inhibits renal cell carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4387. doi:10.1158/1538-7445.AM2014-4387