The Oncogene Modulates Glycolytic and Invasive Genes to Enhance Cell Viability and Migration in Human Retinoblastoma.

Retinoblastoma is usually initiated by biallelic gene inactivation. In addition, copy number alterations also contribute to RB pathogenesis. However, expression, its role in disease progression and correlation with RB histological risk factors are not well understood. We studied the expression of in enucleated RB patient specimens by immunohistochemistry. is overexpressed in RB compared to control retina. Our microarray gene expression analysis followed by qRT-PCR validation revealed that genes involved in glucose metabolism and migration are significantly downregulated in knockdown cells. Further, targeting in RB cells using small molecule compounds or shRNAs led to decreased cell survival and migration, increased apoptosis and cell cycle arrest, suggesting that inhibition can be a potential therapeutic strategy. We also noted that inhibition results in reduction in glucose uptake, lactate production, ROS levels and gelatinolytic activity of active-MMP9, explaining a possible mechanism of in RB. Taking clues from our findings, we tested a combination treatment of RB cells with carboplatin and inhibitors to find enhanced therapeutic efficacy compared to single drug treatment. Thus, inhibition can be a potential therapeutic strategy in combination with existing chemotherapy drugs to restrict tumor cell growth in RB.