Cancers, Vol. 13, Pages 5248: The Oncogene MYCN Modulates Glycolytic and Invasive Genes to Enhance Cell Viability and Migration in Human Retinoblastoma

Cancers, Vol. 13, Pages 5248: The Oncogene MYCN Modulates Glycolytic and Invasive Genes to Enhance Cell Viability and Migration in Human Retinoblastoma Cancers doi: 10.3390/cancers13205248 Authors: Swatishree Sradhanjali Padmalochan Rout Devjyoti Tripathy Swathi Kaliki Suryasnata Rath Rahul Modak Ruchi Mittal Tirumala Kumar Chowdary Mamatha M. Reddy Retinoblastoma is usually initiated by biallelic RB1 gene inactivation. In addition, MYCN copy number alterations also contribute to RB pathogenesis. However, MYCN expression, its role in disease progression and correlation with RB histological risk factors are not well understood. We studied the expression of MYCN in enucleated RB patient specimens by immunohistochemistry. MYCN 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 MYCN knockdown cells. Further, targeting MYCN in RB cells using small molecule compounds or shRNAs led to decreased cell survival and migration, increased apoptosis and cell cycle arrest, suggesting that MYCN inhibition can be a potential therapeutic strategy. We also noted that MYCN inhibition results in reduction in glucose uptake, lactate production, ROS levels and gelatinolytic activity of active-MMP9, explaining a possible mechanism of MYCN in RB. Taking clues from our findings, we tested a combination treatme...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research