Fedorova Maria S, Snezhkina Anastasiya V, Lipatova Anastasiya V, Pavlov Vladislav S, Kobelyatskaya Anastasiya A, Guvatova Zulfiya G, Pudova Elena A, Savvateeva Maria V, Ishina Irina A, Demidova Tatiana B, Volchenko Nadezhda N, Trofimov Dmitry Y, Sukhikh Gennady T, Krasnov George S, Kudryavtseva Anna V
Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.
A. N. Severtsov Institute of Ecology and Evolution, Russian Academy of Sciences, Moscow, Russia.
Front Genet. 2020 Dec 10;11:594933. doi: 10.3389/fgene.2020.594933. eCollection 2020.
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.
基因（神经纤毛蛋白和类托洛依德蛋白2）编码一种作为红藻氨酸受体辅助亚基的蛋白质，且主要在大脑中表达。在几种肿瘤中已观察到该基因的上调；然而，其在肿瘤发生中的作用仍不清楚。在本研究中，我们使用定量PCR（qPCR）研究了该基因在乳腺癌、前列腺癌和结直肠癌中的表达，以及短发夹RNA（shRNA）介导的该基因沉默对结肠癌细胞转录组变化的影响。在所研究的肿瘤中，我们观察到该基因的mRNA水平既有升高也有降低，且与主要临床病理特征无相关性。在HCT116细胞中，该基因的敲低导致17个基因和2个长链非编码RNA（lncRNA）的差异表达，这些基因与昼夜节律的上调以及包括Wnt、转化生长因子（TGF）-β、Janus激酶（JAK）-信号转导子和转录激活子（STAT）、丝裂原活化蛋白激酶（MAPK）以及磷脂酰肌醇3激酶（PI3K）/蛋白激酶B（AKT）通路在内的几种癌症相关通路的下调有关。此外，我们证明了利用一种新型模式生物——短命鱼类来评估该基因功能的可能性。该鱼类中的直系同源基因在核苷酸和氨基酸序列上与人的该基因具有高度相似性，并且在各种鱼类组织中具有稳定表达的特征。总的来说，我们的研究结果表明该基因在乳腺癌、前列腺癌和结直肠癌中失调，并且主要通过细胞信号传导参与肿瘤发展。
