NETO2 Is Deregulated in Breast, Prostate, and Colorectal Cancer and Participates in Cellular Signaling

The gene (neuropilin and tolloid-like 2) encodes a protein that acts as an accessory subunit of kainate receptors and is predominantly expressed in the brain. Upregulation of has been observed in several tumors; however, its role in tumorigenesis remains unclear. In this study, we investigated expression in breast, prostate, and colorectal cancer using quantitative PCR (qPCR), as well as the effect of shRNA-mediated silencing on transcriptome changes in colorectal cancer cells. In the investigated tumors, we observed both increased and decreased mRNA levels, presenting no correlation with the main clinicopathological characteristics. In HCT116 cells, knockdown resulted in the differential expression of 17 genes and 2 long non-coding RNAs (lncRNAs), associated with the upregulation of circadian rhythm and downregulation of several cancer-associated pathways, including Wnt, transforming growth factor (TGF)-β, Janus kinase (JAK)-signal transducer and activator of transcription (STAT), mitogen-activated protein kinase (MAPK), and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathways. Furthermore, we demonstrated the possibility to utilize a novel model organism, short-lived fish , for evaluating functions. The ortholog in demonstrated a high similarity in nucleotide and amino acid sequences with human , as well as was characterized by stable expression in various fish tissues. Collectively, our findings demonstrate the deregulation of in the breast, prostate, and colorectal cancer and its participation in the tumor development primarily through cellular signaling.