부산대학교 도서관

Simple Summary: Mutation of the RB1 tumor suppressor gene is fundamental in retinoblastoma initiation and progression although its downstream mechanism has not been well elucidated. Here, we found that expression of proline/arginine-rich end leucine-rich repeat protein (PRELP) is strongly downregulated in human retinoblastoma and highly expressed in Müller glial cells in normal retina. Deletion of PRELP in mice resulted in retinal dysplasia associated with enhanced proliferation. mRNA expression profiling revealed that cancer pathways were strongly activated in PRELP−/− retina. Additionally, cell–cell adhesion was inhibited while epithelial mesenchymal transition (EMT) and inflammation were activated. On the other hand, application of PRELP protein to retinoblastoma cell lines enhances cell–cell and cell–substrate adhesion and inhibits anchorage independent growth by reversing EMT. These observations indicate that PRELP downregulation in human retinoblastoma can contribute cancer progression through regulation of cell adhesion and EMT suggested that PRELP application might be a novel strategy for retinoblastoma treatment. Retinoblastoma (RB) is the most common intraocular pediatric cancer. Nearly all cases of RB are associated with mutations compromising the function of the RB1 tumor suppressor gene. We previously demonstrated that PRELP is widely downregulated in various cancers and our in vivo and in vitro analysis revealed PRELP as a novel tumor suppressor and regulator of EMT. In addition, PRELP is located at chromosome 1q31.1, around a region hypothesized to be associated with the initiation of malignancy in RB. Therefore, in this study, we investigated the role of PRELP in RB through in vitro analysis and next-generation sequencing. Immunostaining revealed that PRELP is expressed in Müller glial cells in the retina. mRNA expression profiling of PRELP−/− mouse retina and PRELP-treated RB cells found that PRELP contributes to RB progression via regulation of the cancer microenvironment, in which loss of PRELP reduces cell–cell adhesion and facilitates EMT. Our observations suggest that PRELP may have potential as a new strategy for RB treatment. [ABSTRACT FROM AUTHOR]