STAT3 inhibition suppresses proliferation of retinoblastoma through down-regulation of positive feedback loop of STAT3/miR-17-92 clusters.

ABSTRACT: Retinoblastoma, the most common intraocular malignant tumor in children, is characterized by the loss of both functional alleles of RB1 gene, which however alone cannot maintain malignant characteristics of retinoblastoma cells. Nevertheless, the investigation of other molecular aberrations such as matrix metalloproteinases (MMPs) and miRNAs is still lacking. In this study, we demonstrate that STAT3 is activated in retinoblastoma cells, Ki67-positive areas of in vivo orthotopic tumors in BALB/c nude mice, and human retinoblastoma tissues of the advanced stage. Furthermore, target genes of STAT3 including BCL2, BCL2L1, BIRC5, and MMP9 are up-regulated in retinoblastoma cells compared to other retinal constituent cells. Interestingly, STAT3 inhibition by targeted siRNA suppresses the prolife

SUBMITTER: Jo DH 

PROVIDER: S-EPMC4294389 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature