Restoration of miR-29b exerts anti-cancer effects on glioblastoma.

ABSTRACT

BACKGROUND: Glioblastoma multiforme (GBM) is known as one of the most fatal forms of cancer. MicroRNAs have been widely implicated in the regulation of mammalian development and pathogenesis. The brain-enriched miR-29 subfamilies are known to be exclusively expressed in the developing brain, and they are aberrantly down-regulated in GBM. This study aims to elucidate the role of miR-29b in GBM development and the feasibility of therapeutic targeting using conjugated nanoparticles. METHODS: After confirmation of miR-29b expression levels in GBM tissues by analysis of open source data, the anticancer effect of miR-29b was tested by the introduction of syn-hsa-miR-29b-3p in the A172 GBM cell line. In vitro studies of cell viability and apoptosis and ex vivo study using GBM tissue slice cultures from 3 patients and nanoparticle delivery of miR-29b were performed. RESULTS: We discovered an increase in apoptotic cell populations with the introduction of miR-29b in the GBM cell line. An established human-derived GBM tissue slice culture system confirmed the anticancer effect of miR-29b-conjugated nanoparticles. Using PCR array, we found that exogenous miR-29b inhibits the expression of COL1A2, COL3A1, COL4A1, ELN, ITGA11, MMP24, and SPARC, which mediates an anticancer effect. CONCLUSIONS: miR-29b may serve as a putative therapeutic molecule when its expression is restored using a nanoparticle delivery system in GBM.