Targeting HMGA2 in Retinoblastoma Cells in vitro Using the Aptamer Strategy

摘要

High-mobility group A2 (HMGA2) protein regulates retinoblastoma (RB) cancer cell proliferation. Here, a stable phos-phorothioate-modified HMGA2 aptamer was used to block HMGA2 protein function in RB cells. HMGA2-aptamer inter-nalisation in RB cells (Y79, Weri Rb1) and non-neoplastic human retinal cells (MI0-M1) were optimised. Aptamer induced dose-dependent cytotoxicity in RB cancer cells (0.25-1.5 um). Increased expression of TGFfi, SMAD4, CDH1, BAX, CASP3, PARP mRNA and decreased SNAI1, Bd2 mRNA levels in aptamer-treated RB cells suggests the activation of TGFbeta-SAMD4-mediated apoptotic pathway. Synergistic effect with etoposide was observed in aptamer treated RB cells (p value <0.05). No significant toxicity was observed in non-neoplastic retinal cells.