METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
方法:进行信使RNA(mRNA)和微小RNA(miRNA)测序的整合分析以确定外泌体衍生的miRNA和mRNA在人RTK衍生的细胞系和人胚肾细胞系中的表达谱。进行基因本体富集分析以分析RTK细胞中差异表达的mRNA的功能特征。进行基质胶侵袭和伤口愈合测定以评估细胞侵袭和迁移能力。
结果:40种mRNA在RTK细胞中高表达,其在RTK细胞中的表达低于对照。这些mRNA主要与细胞粘附有关。在这些mRNA中,我们选择神经纤毛蛋白1(NRP1)作为候选癌基因,因为它的上调表达与几种肿瘤的不良预后相关.敲低NRP1的RTK细胞表现出降低的侵袭和迁移能力。
结论:我们的研究表明,NRP1通过促进RTK细胞的侵袭和迁移而充当癌基因,并且它可以作为治疗靶标。