Lian Shuaibin, Li Liansheng, Zhou Yongjie, Liu Zixiao, Wang Lei
College of Physics and Electronic Engineering, XinYang Normal University, Xinyang, HeNan, China.
College of Life Sciences, XinYang Normal University, Xinyang, HeNan, China.
PeerJ. 2019 Sep 17;7:e7696. doi: 10.7717/peerj.7696. eCollection 2019.
RNA-binding proteins (RBPs) play important roles in cellular homeostasis by regulating the expression of thousands of transcripts, which have been reported to be involved in human tumorigenesis. Despite previous reports of the dysregulation of RBPs in cancers, the degree of dysregulation of RBPs in cancers and the intrinsic relevance between dysregulated RBPs and clinical TNM information remains unknown. Furthermore, the co-expressed networks of dysregulated RBPs with transcriptional factors and lncRNAs also require further investigation.
Here, we firstly analyzed the deviations of expression levels of 1,542 RBPs from 20 cancer types and found that (1) RBPs are dysregulated in almost all 20 cancer types, especially in BLCA, COAD, READ, STAD, LUAD, LUSC and GBM with proportion of deviation larger than 300% compared with non-RBPs in normal tissues. (2) Up- and down-regulated RBPs also show opposed patterns of differential expression in cancers and normal tissues. In addition, down-regulated RBPs show a greater degree of dysregulated expression than up-regulated RBPs do. Secondly, we analyzed the intrinsic relevance between dysregulated RBPs and clinical TNM information and found that (3) Clinical TNM information for two cancer types-CHOL and KICH-is shown to be closely related to patterns of differentially expressed RBPs (DE RBPs) by co-expression cluster analysis. Thirdly, we identified ten key RBPs (seven down-regulated and three up-regulated) in CHOL and seven key RBPs (five down-regulated and two up-regulated) in KICH by analyzing co-expression correlation networks. Fourthly, we constructed the co-expression networks of key RBPs between 1,570 TFs and 4,147 lncRNAs for CHOL and KICH, respectively.
These results may provide an insight into the understanding of the functions of RBPs in human carcinogenesis. Furthermore, key RBPs and the co-expressed networks offer useful information for potential prognostic biomarkers and therapeutic targets for patients with cancers at the and stages in two cancer types CHOL and KICH.
RNA结合蛋白(RBPs)通过调控数千种转录本的表达在细胞稳态中发挥重要作用,据报道这些转录本参与了人类肿瘤发生。尽管先前有关于癌症中RBPs失调的报道,但RBPs在癌症中的失调程度以及失调的RBPs与临床TNM信息之间的内在相关性仍不清楚。此外,失调的RBPs与转录因子和长链非编码RNA(lncRNAs)的共表达网络也需要进一步研究。
在此,我们首先分析了来自20种癌症类型的1542个RBPs的表达水平偏差,发现:(1)几乎在所有20种癌症类型中RBPs都失调,尤其是在膀胱癌(BLCA)、结肠癌(COAD)、直肠癌(READ)、胃癌(STAD)、肺腺癌(LUAD)、肺鳞癌(LUSC)和胶质母细胞瘤(GBM)中,与正常组织中的非RBPs相比,偏差比例大于300%。(2)上调和下调的RBPs在癌症组织和正常组织中也呈现出相反的差异表达模式。此外,下调的RBPs显示出比上调的RBPs更大程度的失调表达。其次,我们分析了失调的RBPs与临床TNM信息之间的内在相关性,发现:(3)通过共表达聚类分析表明,两种癌症类型——胆管癌(CHOL)和肾嫌色细胞癌(KICH)的临床TNM信息与差异表达的RBPs(DE RBPs)模式密切相关。第三,通过分析共表达相关网络,我们在CHOL中鉴定出10个关键RBPs(7个下调和3个上调),在KICH中鉴定出7个关键RBPs(5个下调和2个上调)。第四,我们分别构建了CHOL和KICH中关键RBPs与1570个转录因子(TFs)和4147个lncRNAs之间的共表达网络。
这些结果可能为深入理解RBPs在人类致癌作用中的功能提供见解。此外,关键RBPs及其共表达网络为胆管癌(CHOL)和肾嫌色细胞癌(KICH)这两种癌症处于[具体阶段1]和[具体阶段2]的患者的潜在预后生物标志物和治疗靶点提供了有用信息。