Up-regulation of CTD-2547G23.4 in hepatocellular carcinoma tissues and its prospective molecular regulatory mechanism: a novel qRT-PCR and bioinformatics analysis study.
Up-regulation of CTD-2547G23.4 in hepatocellular carcinoma tissues and its prospective molecular regulatory mechanism: a novel qRT-PCR and bioinformatics analysis study.
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DOI：
10.1186/s12935-018-0566-3
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发表时间：
2018
影响因子：
5.8
通讯作者：
Chen G
中科院分区：
文献类型：
--
作者：
Wen DY;Lin P;Liang HW;Yang X;Li HY;He Y;Yang H;Chen G
据报道，包括肝细胞癌 (HCC) 在内的多种癌症的发病机制和进展中存在长链非编码 RNA (lncRNA) 的表达失调。 LncRNA CTD-2547G23.4是一种新型lncRNA，其在HCC中的作用尚不清楚。在此，我们旨在阐明 CTD-2547G23.4 的表达模式和临床价值，并通过生物信息学分析探讨 HCC 中的前瞻性调控机制。为了识别 HCC 中差异表达的 lncRNA，我们通过癌症基因组图谱 (TCGA) 下载了 HCC 和邻近非肿瘤组织的 RNA-Seq 数据。通过R语言和受试者工作特征曲线分析，选择CTD-2547G23.4。此外，我们通过 Gene Expression Omnibus (GEO)、ArrayExpress、Oncomine 数据库和定量实时聚合酶链反应 (qRT-PCR) 验证了 CTD-2547G23.4 的差异表达。还评估了 CTD-2547G23.4 水平与临床病理参数之间的关系。为了进一步探讨 CTD-2547G23.4 在 HCC 细胞周期中的作用，应用慢病毒介导的小干扰 RNA 来沉默 Huh-7 细胞系中 CTD-2547G23.4 的表达。此外，从癌症非编码RNA图谱（TANRIC）数据库和多实验矩阵（MEM）收集的CTD-2547G23.4相关基因通过基因本体论（GO）、京都基因和基因组百科全书、通过进化关系的蛋白质分析和蛋白质-蛋白质相互作用（PPI）网络进行评估。 TCGA 数据集中，370 个 HCC 组织样本中 CTD-2547G23.4 的表达显着高于邻近非肿瘤肝组织（48.762±27.270 比 14.511±8.341，P<0.001）。实时RT-qPCR评估CTD-2547G23.4在HCC中的相对表达水平始终高于癌旁组织（2.464±0.833 vs. 1.813±0.784，P=0.001）。根据 TCGA、qRT-PCR 和 GEO 数据，汇总受试者工作特征曲线的曲线下面积为 0.8720。进一步分析表明CTD-2547G23.4表达水平的升高与肿瘤的组织学分级和血管瘤细胞类型相关。 CTD-2547G23.4敲除细胞中CTD-2547G23.4的表达显着下调。此外，细胞周期分析表明，Huh-7 细胞系中 CTD-2547G23.4 的缺失导致 S 期停滞。此外，还对 TANRIC 和 MEM 数据库鉴定的 314 个相关基因进行了通路分析。生物信息学分析表明CTD-2547G23.4可能通过SRC、CREBBP、ADCY8和PPARA这4个枢纽基因在HCC的进展中发挥关键作用。总的来说，我们提出了这样的假设：新型lncRNA CTD-2547G23.4可能作为一种特殊的临床指标，并通过各种相关基因促进HCC肿瘤的发生和进展。本文的在线版本 (10.1186/s12935-018-0566-3) 包含补充材料，可供授权用户使用。
Dysregulated expression of long non-coding RNAs (lncRNAs) has been reported in the pathogenesis and progression of multiple cancers, including hepatocellular carcinoma (HCC). LncRNA CTD-2547G23.4 is a novel lncRNA, and its role in HCC is still unknown. Here, we aimed to clarify the expression pattern and clinical value of CTD-2547G23.4 and to investigate the prospective regulatory mechanism via bioinformatics analysis in HCC. To identify differentially expressed lncRNAs in HCC, we downloaded RNA-Seq data for HCC and adjacent non-tumour tissues via The Cancer Genome Atlas (TCGA). CTD-2547G23.4 was selected by using the R language and receiver operating characteristic curve analysis. Furthermore, we validated the differential expression of CTD-2547G23.4 via Gene Expression Omnibus (GEO), ArrayExpress, Oncomine databases and quantitative real-time polymerase chain reaction (qRT-PCR). The relationship between the CTD-2547G23.4 level and clinic pathological parameters was also assessed. To further probe the role of CTD-2547G23.4 in HCC cell cycle, lentivirus-mediated small interfering RNA was applied to silence CTD-2547G23.4 expression in Huh-7 cell line. In addition, the related genes of CTD-2547G23.4 gathered from The Atlas of Noncoding RNAs in Cancer (TANRIC) database and Multi Experiment Matrix (MEM) were assessed with Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes, Protein Analysis Through Evolutionary Relationships and protein–protein interaction (PPI) networks. CTD-2547G23.4 expression was remarkably higher in 370 HCC tissue samples than that in adjacent non-tumour liver tissues (48.762 ± 27.270 vs. 14.511 ± 8.341, P < 0.001) from TCGA dataset. The relative expression level of CTD-2547G23.4 in HCC was consistently higher than that in adjacent non-cancerous tissues (2.464 ± 0.833 vs. 1.813 ± 0.784, P = 0.001) as assessed by real time RT-qPCR. The area under the curve of the summary receiver operating characteristic curve was 0.8720 based on TCGA, qRT-PCR and GEO data. Further analysis indicated that the increased expression levels of CTD-2547G23.4 were associated with the neoplasm histologic grade and vascular tumour cell type. The expression of CTD-2547G23.4 was significantly downregulated in CTD-2547G23.4 knockdown cells. Moreover, cell cycle analysis revealed that CTD-2547G23.4 depletion in Huh-7 cell line led to S phase arrest. Furthermore, 314 related genes identified by TANRIC and MEM databases were processed with a pathway analysis. The bioinformatics analysis indicated that CTD-2547G23.4 might play a key role in the progress of HCC through four hub genes, SRC, CREBBP, ADCY8 and PPARA. Collectively, we put forward the hypothesis that the novel lncRNA CTD-2547G23.4 may act as an exceptional clinical index and promote the HCC tumourigenesis and progression via various related genes. The online version of this article (10.1186/s12935-018-0566-3) contains supplementary material, which is available to authorized users.
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影响因子：
12.3
作者：
Adler P;Kolde R;Kull M;Tkachenko A;Peterson H;Reimand J;Vilo J
通讯作者：
Vilo J
影响因子：
254.7
作者：
Siegel, Rebecca;Ma, Jiemin;Jemal, Ahmedin
通讯作者：
Jemal, Ahmedin
DOI：
10.1016/j.bpg.2014.08.007
发表时间：
2014-10-01
影响因子：
3.2
作者：
Bosetti, Cristina;Turati, Federica;La Vecchia, Carlo
通讯作者：
La Vecchia, Carlo
影响因子：
3.7
作者：
Ku CY;Wang YR;Lin HY;Lu SC;Lin JY
通讯作者：
Lin JY
影响因子：
3.5
作者：
Contreras, Alejandra V.;Rangel-Escareno, Claudia;Tovar, Armando R.
通讯作者：
Tovar, Armando R.