miRNA profiling of esophageal adenocarcinoma using transcriptome analysis.

IF 2.2 4区 医学 Q3 ONCOLOGY
Ryan Corlett, Charles Button, Sydney Scheel, Swati Agrawal, Vikrant Rai, Kalyana C Nandipati
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引用次数: 0

Abstract

Esophageal adenocarcinoma (EAC) occurs following a series of histological changes through epithelial-mesenchymal transition (EMT). A variable expression of normal and aberrant genes in the tissue can contribute to the development of EAC through the activation or inhibition of critical molecular signaling pathways. Gene expression is regulated by various regulatory factors, including transcription factors and microRNAs (miRs). The exact profile of miRs associated with the pathogenesis of EAC is largely unknown, though some candidate miRNAs have been reported in the literature. To identify the unique miR profile associated with EAC, we compared normal esophageal tissue to EAC tissue using bulk RNA sequencing. RNA sequence data was verified using qPCR of 18 selected genes. Fourteen were confirmed as being upregulated, which include CDH11, PCOLCE, SULF1, GJA4, LUM, CDH6, GNA12, F2RL2, CTSZ, TYROBP, and KDELR3 as well as the downregulation of UGT1A1. We then conducted Ingenuity Pathway Analysis (IPA) to analyze for novel miR-gene relationships through Causal Network Analysis and Upstream Regulator Analysis. We identified 46 miRs that were aberrantly expressed in EAC compared to control tissues. In EAC tissues, seven miRs were associated with activated networks, while 39 miRs were associated with inhibited networks. The miR-gene relationships identified provide novel insights into potentially oncogenic molecular pathways and genes associated with carcinogenesis in esophageal tissue. Our results revealed a distinct miR profile associated with dysregulated genes. The miRs and genes identified in this study may be used in the future as biomarkers and serve as potential therapeutic targets in EAC.

利用转录组分析法绘制食管腺癌的 miRNA 图谱
食管腺癌(EAC)是通过上皮-间质转化(EMT)发生一系列组织学变化而形成的。组织中正常基因和异常基因的不同表达可通过激活或抑制关键的分子信号通路导致 EAC 的发生。基因表达受各种调节因子的调控,包括转录因子和微RNA(miRs)。尽管文献中已报道了一些候选 miRNAs,但与 EAC 发病机制相关的 miRs 的确切特征在很大程度上仍不清楚。为了确定与 EAC 相关的独特 miR 特征,我们使用批量 RNA 测序法比较了正常食管组织和 EAC 组织。通过对 18 个选定基因进行 qPCR 验证了 RNA 序列数据。其中 14 个基因被证实上调,包括 CDH11、PCOLCE、SULF1、GJA4、LUM、CDH6、GNA12、F2RL2、CTSZ、TYROBP 和 KDELR3,以及 UGT1A1 的下调。然后,我们通过因果网络分析(Causal Network Analysis)和上游调控因子分析(Upstream Regulator Analysis)进行了Ingenuity Pathway Analysis(IPA),以分析新的miR与基因的关系。与对照组织相比,我们发现了 46 个在 EAC 中异常表达的 miRs。在 EAC 组织中,7 个 miR 与激活网络相关,39 个 miR 与抑制网络相关。所发现的 miR 与基因的关系为了解食管组织中潜在的致癌分子通路和与癌变相关的基因提供了新的视角。我们的研究结果揭示了与失调基因相关的独特 miR 图谱。本研究发现的 miRs 和基因将来可用作生物标记物,并成为 EAC 的潜在治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Cancer Biomarkers
Cancer Biomarkers ONCOLOGY-
CiteScore
5.20
自引率
3.20%
发文量
195
审稿时长
3 months
期刊介绍: Concentrating on molecular biomarkers in cancer research, Cancer Biomarkers publishes original research findings (and reviews solicited by the editor) on the subject of the identification of markers associated with the disease processes whether or not they are an integral part of the pathological lesion. The disease markers may include, but are not limited to, genomic, epigenomic, proteomics, cellular and morphologic, and genetic factors predisposing to the disease or indicating the occurrence of the disease. Manuscripts on these factors or biomarkers, either in altered forms, abnormal concentrations or with abnormal tissue distribution leading to disease causation will be accepted.
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