MicroRNA-124-3p expression and its prospective functional pathways in hepatocellular carcinoma: A quantitative polymerase chain reaction, gene expression omnibus and bioinformatics study.

MicroRNA-124-3p expression and its prospective functional pathways in hepatocellular carcinoma: A quantitative polymerase chain reaction, gene expression omnibus and bioinformatics study.
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DOI:
10.3892/ol.2018.8045
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发表时间:
2018-04
期刊:
影响因子:
2.9
通讯作者:
Ma J
Ma J
中科院分区:
医学4区
文献类型:
--
作者:
He RQ;Yang X;Liang L;Chen G;Ma J

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本研究旨在探讨microRNA(miR)-124-3p在肝细胞癌(HCC)发生发展中的潜在临床意义,以及HCC功能通路的潜在靶基因。采用逆转录-定量聚合酶链反应(RT-PCR)检测101例HCC及癌旁组织中miR-124- 3 p的表达。此外,还分析了miR-124- 3 p表达与临床参数之间的关联。整合miR-124- 3 p转染后鉴定的差异表达基因、计算机预测的潜在靶基因和自然语言处理(NLP)获得的HCC关键基因,获得miR-124- 3 p在HCC中的潜在靶基因。通过蛋白质-蛋白质相互作用(PPI)网络、基因本体(GO)富集分析、京都基因和基因组百科全书(KEGG)和通过进化关系的蛋白质注释(PANTHER)途径富集分析评估相关信号通路。miR-124- 3 p在HCC组织中的表达与在邻近非癌肝组织中的表达相比显著降低。在HCC中,miR-124- 3 p被证明与临床分期相关。miR-124- 3 p低表达组的平均生存时间较高表达组缩短。差异表达基因、miR-124- 3 p预测靶基因和NLP鉴定基因共132个基因重叠。PPI网络构建共显示109个节点和386条边,并确定了20个关键基因。GO的3个分类的主要富集术语包括细胞增殖的调节、细胞生物合成过程的正调节、细胞前沿、胞质溶胶和细胞突起、蛋白激酶活性、转录激活因子活性和酶结合。KEGG分析显示,胰腺癌、前列腺癌和非小细胞肺癌是前三名。血管生成、内皮生长因子受体信号通路和成纤维细胞生长因子信号通路被确定为PANTHER通路分析中最重要的术语。本研究证实miR-124- 3 p在HCC中起肿瘤抑制剂的作用。miR-124- 3 p可以靶向多个基因,在时空上发挥其作用,或与HCC中的各种过程组合。miR-124- 3 p靶点的功能表征将为HCC进展中发生的分子变化提供新的见解。
The present study aimed to explore the potential clinical significance of microRNA (miR)-124-3p expression in the hepatocarcinogenesis and development of hepatocellular carcinoma (HCC), as well as the potential target genes of functional HCC pathways. Reverse transcription-quantitative polymerase chain reaction was performed to evaluate the expression of miR-124-3p in 101 HCC and adjacent non-cancerous tissue samples. Additionally, the association between miR-124-3p expression and clinical parameters was also analyzed. Differentially expressed genes identified following miR-124-3p transfection, the prospective target genes predicted in silico and the key genes of HCC obtained from Natural Language Processing (NLP) were integrated to obtain potential target genes of miR-124-3p in HCC. Relevant signaling pathways were assessed with protein-protein interaction (PPI) networks, Gene Ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Protein Annotation Through Evolutionary Relationships (PANTHER) pathway enrichment analysis. miR-124-3p expression was significantly reduced in HCC tissues compared with expression in adjacent non-cancerous liver tissues. In HCC, miR-124-3p was demonstrated to be associated with clinical stage. The mean survival time of the low miR-124-3p expression group was reduced compared with that of the high expression group. A total of 132 genes overlapped from differentially expressed genes, miR-124-3p predicted target genes and NLP identified genes. PPI network construction revealed a total of 109 nodes and 386 edges, and 20 key genes were identified. The major enriched terms of three GO categories included regulation of cell proliferation, positive regulation of cellular biosynthetic processes, cell leading edge, cytosol and cell projection, protein kinase activity, transcription activator activity and enzyme binding. KEGG analysis revealed pancreatic cancer, prostate cancer and non-small cell lung cancer as the top three terms. Angiogenesis, the endothelial growth factor receptor signaling pathway and the fibroblast growth factor signaling pathway were identified as the most significant terms in the PANTHER pathway analysis. The present study confirmed that miR-124-3p acts as a tumor suppressor in HCC. miR-124-3p may target multiple genes, exerting its effect spatiotemporally, or in combination with a diverse range of processes in HCC. Functional characterization of miR-124-3p targets will offer novel insight into the molecular changes that occur in HCC progression.
DOI: 10.1002/ijc.28075
发表时间: 2013-08-15
影响因子: 6.4
作者:
Diaz, Giacomo;Melis, Marta;Tice, Ashley;Kleiner, David E.;Mishra, Lopa;Zamboni, Fausto;Farci, Patrizia
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