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对差异表达的环状RNA进行综合分析,揭示了胰腺导管腺癌中的一个竞争性内源RNA网络。

Comprehensive analysis of differentially expressed circRNAs revealed a ceRNA network in pancreatic ductaladenocarcinoma.

作者信息

Zhou Jin-Zhe, Hu Mu-Ren, Diao Hong-Liang, Wang Qi-Wei, Huang Qi, Ge Bu-Jun

机构信息

Department of General Surgery, Tongji Hospital, Tongji University School of Medicine, Shanghai, China.

Department of General Surgery, Karamay Central Hospital, Karamay, Xinjiang, China.

出版信息

Arch Med Sci. 2019 Jul;15(4):979-991. doi: 10.5114/aoms.2019.85204. Epub 2019 May 15.

DOI:10.5114/aoms.2019.85204
PMID:31360192
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6657245/
Abstract

INTRODUCTION

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest malignancies. However, the molecular mechanisms underlying PDAC are still not completely understood. Circular RNAs (circRNAs) are a unique class of RNA formed by special loop splicing. More and more researchers have paid attention to circRNAs.

MATERIAL AND METHODS

In this study, we constructed a circRNA-mediated competing endogenous RNA (ceRNA) network in PDAC. Gene ontology (GO) analysis was performed to explore circRNAs' potential roles in PDAC progression. We also constructed an up-stream transcriptional network of circRNAs' parental genes and found that many transcription factors (TFs), such as tumor protein p53 (TP53) and MYC, could regulate their expression.

RESULTS

This study, which aimed to identify differentially expressed circRNAs in PDAC, suggested that circRNAs may also act as biomarkers for PDAC. We analyzed two public datasets (GSE69362 and GSE79634) to identify differentially expressed circRNAs in PDAC. Finally, we found that DExH-Box Helicase 9 (DHX9) may be a potential regulator of circRNA formation in PDAC. Genomic loci of four down-regulated circRNAs - hsa_circ_000691, hsa_circ_0049392, hsa_circ_0005203, and hsa_circ_0001626 - contained DHX9 binding sites, suggesting that they may be directly regulated by DHX9.

CONCLUSIONS

Our study identified differentially expressed circRNAs in PDAC, suggesting that circRNAs may also act as biomarkers for PDAC. Additional investigations of function and up-stream regulation of differentially expressed circRNA in PDAC are still needed.

摘要

引言

胰腺导管腺癌(PDAC)是最致命的恶性肿瘤之一。然而,PDAC潜在的分子机制仍未完全明确。环状RNA(circRNAs)是一类由特殊环化剪接形成的独特RNA。越来越多的研究者开始关注circRNAs。

材料与方法

在本研究中,我们构建了PDAC中circRNA介导的竞争性内源RNA(ceRNA)网络。进行基因本体(GO)分析以探究circRNAs在PDAC进展中的潜在作用。我们还构建了circRNAs亲本基因的上游转录网络,发现许多转录因子(TFs),如肿瘤蛋白p53(TP53)和MYC,可调节它们的表达。

结果

本研究旨在鉴定PDAC中差异表达的circRNAs,提示circRNAs也可能作为PDAC的生物标志物。我们分析了两个公共数据集(GSE69362和GSE79634)以鉴定PDAC中差异表达的circRNAs。最后,我们发现解旋酶9(DHX9)可能是PDAC中circRNA形成的潜在调节因子。四个下调的circRNAs——hsa_circ_000691、hsa_circ_0049392、hsa_circ_0005203和hsa_circ_0001626——的基因组位点包含DHX9结合位点,表明它们可能受DHX9直接调控。

结论

我们的研究鉴定了PDAC中差异表达的circRNAs,提示circRNAs也可能作为PDAC的生物标志物。仍需对PDAC中差异表达circRNA的功能及上游调控进行进一步研究。

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