Genistein suppresses retinoblastoma cell viability and growth and induces apoptosis by upregulating miR-145 and inhibiting its target ABCE1.

PURPOSE

Retinoblastoma is a rare malignancy in developing retina tissue in children with limited therapeutic options. Here we sought to investigate the potential clinical value of genistein, the phytoestrogen derived from the soybean with antioxidant activity, in this disease.

METHODS

Retinoblastoma cells were treated with genistein. Colony formation capacity was measured with soft agar assay. MiRNA was identified with microarray. Post-transcriptional regulation of gene expression was determined with dual-luciferase reporter assay. Cell proliferation and apoptosis were measured with the Cell Counting Kit-8 (CCK-8) method and annexin V-propidium iodide (PI) staining. The xenograft model was administered with genistein, and tumor growth was monitored.

RESULTS

The results showed that genistein treatment significantly suppressed proliferation and anchorage-independent growth of the human retinoblastoma cell line Y79 in vitro, which partially attributed to apoptosis induction. MicroRNA array screening identified that miR-145 was upregulated by genistein. Through post-transcriptional regulation of ABCE1, miR-145 functioned as a key downstream effector in genistein-mediated tumor suppression in retinoblastoma. Moreover, the in vivo data consolidated the inhibitory effect of genistein against retinoblastoma xenograft via upregulation of miR-145.

CONCLUSIONS

The data highlighted the therapeutic potency of genistein in this disease and showed that further clinical investigation is warranted.