Abstract 3531: MicroRNA delivery by bionanoparticles: regulation of the liver cancer susceptibility gene MICA expression in hepatocytes

Abstract

Abstract Hepatocellular carcinoma (HCC) is an important issue to public health of the world. We recently reported by genome wide association study (GWAS) analyses that a single nucleotide polymorphism (SNP) in the promoter region of the MHC class I polypeptide-related sequence A (MICA) gene that is significantly associated with the risk of hepatitis-virus-related HCC. Because there was a correlation between the expression levels of MICA in the serum depending on the different alleles at the SNP site and the risk of HCC, regulation of MICA expression levels may be useful in the prevention of HCC. Here we show that MICA protein expression in HCC cells can be regulated by the microRNA (miR) 25-93-106b cluster. By use of luciferase assay and FACS analyses, it was confirmed that forced expression of the miR 25-93-106b cluster significantly suppressed MICA expression, whereas inhibition of this miR cluster increased MICA expression in cells that stably express MICA. Furthermore, to deliver efficiently miRNAs into hepatocytes specifically, we developed bio-nanocapsules containing miR93 inside, utilizing hepatitis B virus envelope L-protein. MICA expression levels were indeed suppressed after the delivery of miR93 by these bionanoparticles into hepatocytes. Besides, the binding ability of NKG2D (a receptor of MICA) and in vivo cell-killing by NK cells were changed proportionally to miRNA-induced MICA expression levels. These results suggest that the modulation of MICA expression levels in hepatocytes by delivering miRNAs using these bionanocapsules may be a novel and effective approach to prevent hepatitis-virus-related HCC. Citation Format: Motoko Ohno, Motoyuki Otsuka, Takahiro Kishikawa, Takeshi Yoshikawa, Akemi Takata, Kazuhiko Koike. MicroRNA delivery by bionanoparticles: regulation of the liver cancer susceptibility gene MICA expression in hepatocytes. [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 3531. doi:10.1158/1538-7445.AM2014-3531