Department of Pediatric Surgery, Nihon University School of Medicine, 30-1 Oyaguchi-Kamicho, Itabashi, Tokyo, 173-0032, Japan.
Department of Pediatric Surgery, Jichi Medical University, Saitama Medical Center, 1-847, Amanumacho, Omiya, Saitama, 330-8503, Japan.
Pediatr Surg Int. 2024 Aug 12;40(1):221. doi: 10.1007/s00383-024-05808-8.
The aim of this study was to detect candidate oncogenes of rhabdoid tumor of the kidney (RTK) and evaluate their roles in RTK in vitro.
An integrated analysis of messenger RNA (mRNA) and microRNA (miRNA) sequencing was performed to determine the expression profile of exosome-derived miRNAs and mRNAs in human RTK-derived cell lines and a human embryonic renal cell line. A Gene Ontology enrichment analysis was performed to analyze the functional characteristics of differentially expressed mRNAs in RTK cells. Matrigel invasion and wound-healing assays were performed to evaluate the cell invasion and migration abilities.
Forty mRNAs were highly expressed in RTK cells targeted by exosomal miRNAs, the expression of which was lower in RTK cells than in the controls. These mRNAs were primarily related to cell adhesion. Of these mRNAs, we selected neuropilin 1 (NRP1) as a candidate oncogene because its upregulated expression is associated with a poor prognosis of several types of tumors. RTK cells in which NRP1 had been knocked down exhibited decreased invasive and migratory abilities.
Our study indicates that NRP1 acts as an oncogene by promoting the invasion and migration of RTK cells and that it could serve as a therapeutic target.
本研究旨在检测肾横纹肌样瘤(RTK)的候选癌基因,并评估其在 RTK 中的体外作用。
通过信使 RNA(mRNA)和 microRNA(miRNA)测序的综合分析,确定人 RTK 衍生细胞系和人胚胎肾细胞系中外泌体衍生的 miRNA 和 mRNA 的表达谱。进行基因本体论富集分析以分析 RTK 细胞中差异表达的 mRNAs 的功能特征。进行 Matrigel 侵袭和划痕愈合试验以评估细胞侵袭和迁移能力。
40 个 mRNAs 在受外泌体 miRNA 靶向的 RTK 细胞中高表达,其在 RTK 细胞中的表达低于对照组。这些 mRNAs 主要与细胞黏附有关。在这些 mRNAs 中,我们选择神经纤毛蛋白 1(NRP1)作为候选癌基因,因为其上调表达与几种类型肿瘤的不良预后相关。NRP1 被敲低的 RTK 细胞表现出侵袭和迁移能力降低。
我们的研究表明,NRP1 通过促进 RTK 细胞的侵袭和迁移而起癌基因作用,并且它可能成为治疗靶点。