Circular RNA In Invasive and Recurrent Clinical Nonfunctioning Pituitary Adenomas: Expression Profiles and Bioinformatic Analysis

Circular RNA In Invasive and Recurrent Clinical Nonfunctioning Pituitary Adenomas: Expression Profiles and Bioinformatic Analysis
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侵袭性和复发性临床无功能垂体腺瘤中的环状 RNA:表达谱和生物信息学分析

DOI:
10.1016/j.wneu.2018.06.038
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发表时间:
2018-09-01
期刊:
影响因子:
2
通讯作者:
Li, Chuzhong
Li, Chuzhong
中科院分区:
医学4区
文献类型:
--
作者:
Wang, Jianpeng;Wang, Dong;Li, Chuzhong

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背景:临床无功能垂体腺瘤(NFA)的侵袭和复发往往导致手术治疗失败。环状RNAs(CircRNAs)是一类新型的RNAs,其30端和50端连接在一起,在癌症的发生发展中起着重要的作用。方法:应用CircRNA芯片技术检测和总结了10例非侵袭性NFA和65例侵袭性NFA的75例NFA组织和9例复发NFA的9对NFA组织中CircRNA的表达。在此基础上,进行功能浓缩分析和途径分析,利用生物信息学分析工具构建了CircRNA-microRNA(MiRNA)网络。收集5个新的侵袭性NFA样本和5个非侵袭性NFA样本用于芯片检测结果。结果:根据情况(折叠变化2;P<0.05),共鉴定出570个表达异常的CircRNAs(侵袭性肿瘤与非侵袭性肿瘤)和10个上调的CircRNAs(复发肿瘤组织与首次手术肿瘤组织)。侵袭性肿瘤与非侵袭性肿瘤细胞黏附信号转导通路的比较中,发现异常CircRNAs的亲本基因在局部黏附、Hippo信号通路、PI3K-Akt信号通路、黏附连接等细胞黏附信号通路中表达丰富。CircRNA-miRNA网络显示,异常的CircRNA可能作为miRNA海绵发挥作用。结论:这是首次对侵袭性和复发性NFA的CircRNA表达谱进行全面分析的研究。我们的发现将为CircRNAs在NFA的诊断、预后和临床治疗中的意义提供证据。
BACKGROUND: The invasion and recurrence of clinical nonfunctioning pituitary adenomas (NFA) often lead to surgical treatment failure. Circular RNAs (circRNAs) are a novel class of RNAs whose 30 and 50 ends are joined together and have been shown to play important roles in cancer development. Until now, the roles of circRNAs have remained unclear in invasive and recurrent NFA.METHODS: We detected and summarized the circRNA expression pattern in 75 NFA tissues from 10 noninvasive cases and 65 invasive cases and 9 pairs of NFA tumor tissues from 9 recurrent cases by circRNA microarrays. Accordingly, functional enrichment analysis and pathway analysis were performed and the circRNA-microRNA (miRNA) network was generated by bioinformatic analysis tools. Five new invasive NFA samples and 5 noninvasive NFA samples were collected to measure the microarray results.RESULTS: A total of 570 dysregulated circRNAs (invasive tumor vs. noninvasive tumor) and 10 upregulated circRNAs (recurrent tumor tissue vs. first surgery tumor tissue) were identified based on the situation (fold change >2; P < 0.05). The parental genes of the dysregulated circRNAs in the comparison between invasion tumor and noninvasion tumor were found to be enriched in some cell adhesion signaling pathways such as Focal adhesion, Hippo signaling pathway, PI3K-Akt signaling pathway, and Adherens junction. The circRNA-miRNA network showed that the dysregulated circRNA may function as miRNA sponges.CONCLUSIONS: This is the first study to conduct and comprehensively analyze the circRNA expression profile in invasive and recurrent NFA. Our finding will provide evidence for the significance of circRNAs in NFA diagnosis, prognosis, and clinical treatment.