PRELP Regulates Cell-Cell Adhesion and EMT and Inhibits Retinoblastoma Progression.
Jack HopkinsKen AsadaAlex LeungVasiliki PapadakiHongorzul DavaapilMatthew MorrisonTomoko OritaRyohei SekidoHirofumi KosugeM Ashwin ReddyKazuhiro KimuraAkihisa MitaniKouhei TsumotoRyuji HamamotoMandeep S SagooShin-Ichi OhnumaPublished in: Cancers (2022)
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.
Keyphrases
- cell adhesion
- single cell
- epithelial mesenchymal transition
- induced apoptosis
- papillary thyroid
- cell cycle arrest
- genome wide
- stem cells
- oxidative stress
- gene expression
- diabetic retinopathy
- risk assessment
- cell death
- squamous cell
- cell proliferation
- childhood cancer
- spinal cord
- spinal cord injury
- newly diagnosed
- high resolution
- single molecule
- high speed
- data analysis