Comprehensive Analysis of the Expression Profiles of Long Non-Coding RNAs with Associated ceRNA Network Involved in the Colon Cancer Staging and Progression
Comprehensive Analysis of the Expression Profiles of Long Non-Coding RNAs with Associated ceRNA Network Involved in the Colon Cancer Staging and Progression
复制标题
涉及结肠癌分期和进展的长非编码 RNA 及相关 ceRNA 网络的表达谱的综合分析
DOI：
10.1038/s41598-019-52883-2
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发表时间：
2019-11-15
影响因子：
4.6
通讯作者：
Hu, YunZhang
中科院分区：
文献类型：
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作者：
Wu, Meini;Li, Wenliang;Hu, YunZhang
长非编码RNA(LncRNAs)作为竞争内源性RNAs(CeRNAs)与微小RNAs(MiRNAs)在肿瘤的发生和发展中起竞争作用。然而，RNAs及其Cerna网络在结肠癌发生发展过程中的差异表达仍不清楚。本研究旨在对与CC相关的lncRNAs及其Cerna网络进行综合分析。对不同病理阶段的大肠及癌旁正常组织进行全转录组测序。49个lncRNAs在癌组织和癌旁正常组织中均有不同程度表达。TCGA数据库证实了lncRNA CDKN2B-AS1和lncRNA MIR4435-2HG的异常表达。17105个差异表达的mRNA加权基因共表达网络分析显示，模块粉色、午夜蓝、黑色和淡青色的mRNAs与肿瘤组织的TNM和病理分期相关，并且这些mRNAs在肿瘤相关功能和通路中有丰富的表达。由于DElncRNA的变化趋势与DEmRNA相似，而与DEmiRNA相反，因此构建了由3个DEmiRNAs、5个DElncRNAs和130个DEmRNAs组成的Cerna网络。实时荧光定量聚合酶链式反应显示，与I期相比，MEG3在III、IV期肿瘤组织中表达降低，hsa-miR-324-5p表达上调，而FGFR3、PLCB4和IKBKB在癌旁正常组织中表达下调。因此，本研究揭示了LncRNA在CC不同阶段的差异表达，并提示LncRNA CDKN2B-AS1、MIR4435-2HG和MEG3可能作为CC发生发展的诊断生物标志物。
Long non-coding RNAs (lncRNAs) act as competing endogenous RNAs (ceRNAs) to compete with microRNAs (miRNAs) in cancer occurrence and development. However, the differential expression of RNAs and their ceRNA network during the development of colon cancer (CC) remains unclear. This study was aimed at comprehensive analysis of the lncRNAs and their ceRNA networks associated with CC. Whole transcriptome sequencing was performed on colorectal and adjacent normal tissues at different pathological stages. Forty-nine lncRNAs were differently expressed between the CC tissues and their adjacent normal tissues at all stages. Aberrant expression of lncRNA CDKN2B-AS1 and lncRNA MIR4435-2HG was confirmed by TCGA database. Moreover, 14 lncRNAs were differentially expressed between early and advance stages of the tumor tissues, and 117 miRNAs were specifically expressed in stage III & IV. Weighted gene co-expression network analysis of 17105 differently expressed mRNAs revealed that the mRNAs shown in module pink, midnight blue, black, and light cyan were related to TNM and pathological stage, and that these mRNAs were enriched in cancer related functions and pathways. As DElncRNA showed a trend of change similar to that of the DEmRNA and opposite to that of DEmiRNA, ceRNA network was constructed with 3 DEmiRNAs, 5 DElncRNAs, and 130 DEmRNAs. Real time PCR revealed that expression of MEG3 was decreased in the tumor tissues belonging to stage III and IV as compared to that in stage I. Moreover, hsa-miR-324-5p was upregulated, while FGFR3, PLCB4, and IKBKB were downregulated in the tumor tissues as compared to that in the adjacent normal tissues. Thus, this study revealed differentially expressed lncRNA between different stages of CC as well as suggested that lncRNA CDKN2B-AS1, MIR4435-2HG, and MEG3 may act as diagnostic biomarkers for the development of CC.