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

Frontiers in Genetics

Tatiana B. Demidova¹  Maria S. Fedorova²  Maria V. Savvateeva²  George S. Krasnov²  Elena A. Pudova²  Irina A. Ishina²  Anastasiya A. Kobelyatskaya²  Anastasiya V. Lipatova²  Zulfiya G. Guvatova²  Anna V. Kudryavtseva²  Vladislav S. Pavlov²  Anastasiya V. Snezhkina²  Gennady T. Sukhikh³  Dmitry Y. Trofimov³  Nadezhda N. Volchenko⁴ 

[1] A. N. Severtsov Institute of Ecology and Evolution, Russian Academy of Sciences, Moscow, Russia;Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia;National Medical Research Center for Obstetrics, Gynecology and Perinatology Named After Academician V.I. Kulakov, Ministry of Health of the Russian Federation, Moscow, Russia;National Medical Research Radiological Center, Ministry of Health of the Russian Federation, Moscow, Russia;

关键词: NETO2;    breast cancer;    prostate cancer;    colorectal cancer;    fish model;   

DOI  :  10.3389/fgene.2020.594933

来源: DOAJ

【 摘 要 】

The NETO2 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 NETO2 has been observed in several tumors; however, its role in tumorigenesis remains unclear. In this study, we investigated NETO2 expression in breast, prostate, and colorectal cancer using quantitative PCR (qPCR), as well as the effect of shRNA-mediated NETO2 silencing on transcriptome changes in colorectal cancer cells. In the investigated tumors, we observed both increased and decreased NETO2 mRNA levels, presenting no correlation with the main clinicopathological characteristics. In HCT116 cells, NETO2 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 Nothobranchius furzeri, for evaluating NETO2 functions. The ortholog neto2b in N. furzeri demonstrated a high similarity in nucleotide and amino acid sequences with human NETO2, as well as was characterized by stable expression in various fish tissues. Collectively, our findings demonstrate the deregulation of NETO2 in the breast, prostate, and colorectal cancer and its participation in the tumor development primarily through cellular signaling.

【 授权许可】

Unknown