RNA Sequencing and Bioinformatic Analysis on Retinoblastoma Revealing that Cell Cycle Deregulation Is a Key Process in Retinoblastoma Tumorigenesis
RNA Sequencing and Bioinformatic Analysis on Retinoblastoma Revealing that Cell Cycle Deregulation Is a Key Process in Retinoblastoma Tumorigenesis
复制标题
视网膜母细胞瘤的 RNA 测序和生物信息学分析揭示细胞周期失调是视网膜母细胞瘤肿瘤发生的关键过程
DOI：
10.1159/000506993
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发表时间：
2021-02-01
期刊：
影响因子：
2.6
通讯作者：
Lu, Rong
中科院分区：
文献类型：
--
作者：
Nie, Cong;Ma, Huan;Lu, Rong
目的：视网膜母细胞瘤（RB）是一种原发性儿童眼部恶性肿瘤，如果治疗不当可能致命。虽然采用多模式治疗来挽救眼睛，但一些患者可能会出现视力丧失和转移。本研究旨在探索 RB 发病机制的关键途径和因素，这可能成为新型 RB 治疗的潜在靶点。方法：对三个 RB 组织进行 RNA 测序，并以三个正常视网膜为参考。从测序数据中鉴定出差异表达基因（DEG），并通过聚类分析、功能和通路富集、蛋白质-蛋白质相互作用（PPI）和数据挖掘分析进行进一步分析，以筛选致瘤相关性。结果：通过对RB组织进行聚类分析，共鉴定出331个DEG，其表达模式与正常视网膜有显着区别。功能和通路富集以及 PPI 分析共同表明，细胞周期是 RB 组织中发现的最显着上调的通路。经过全面的生物信息学分析，确定了与细胞周期调控相关的六个关键基因，即BUB1、RRM2、TPX2、UBE2C、NUSAP1和DTL。结论：细胞周期通路和6个相关基因可能是RB肿瘤发生的潜在关键因素，为开发新型靶向治疗药物的前瞻性研究奠定了基础。
Purpose: Retinoblastoma (RB) is a primary pediatric ocular malignancy that can be fatal with inadequate treatment. While multimodal treatments are applied for eye salvage, vision loss and metastasis can occur in some patients. The present study aimed to explore key pathways and factors in RB pathogenesis, which could be potential targets for novel RB treatments. Methods: RNA sequencing was performed on three RB tissues and referenced with three normal retinas. Differentially expressed genes (DEGs) were identified from sequencing data and further analyzed with clustering analysis, function and pathway enrichment, protein-protein interaction (PPI), and data-mining analysis in order to screen for tumorigenic relevancy. Results: A total of 331 DEGs were identified by clustering analysis of RB tissues, and the expression patterns were significantly distinguishable from normal retinas. Function and pathway enrichment and PPI analysis together showed that cell cycle was the most prominently upregulated pathway found in RB tissues. Following comprehensive bioinformatic analyses, six key genes relevant to cell cycle regulation were identified, namely BUB1, RRM2, TPX2, UBE2C, NUSAP1, and DTL. Conclusions: Cell cycle pathway and six relevant genes may be potential key factors in RB tumorigenesis and laying the foundation for prospective investigation on development of novel targeted therapies.