Lower expressed miR-198 and its potential targets in hepatocellular carcinoma: a clinicopathological and in silico study.
Lower expressed miR-198 and its potential targets in hepatocellular carcinoma: a clinicopathological and in silico study.
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DOI：
10.2147/ott.s108828
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发表时间：
2016
影响因子：
4
通讯作者：
Dang YW
中科院分区：
文献类型：
--
作者：
Huang WT;Wang HL;Yang H;Ren FH;Luo YH;Huang CQ;Liang YY;Liang HW;Chen G;Dang YW
目的探讨microRNA-198（miR-198）在肝细胞癌（HCC）中的临床病理学意义及可能的作用。收集95例福尔马林固定石蜡包埋的HCC和癌旁肝组织。采用实时定量逆转录聚合酶链反应（RT-PCR）检测miR-198的表达。检测miR-198表达与临床病理特征之间的相关性。同时，从14个miRNA预测数据库和自然语言处理方法中筛选出miR-198在HCC中的潜在靶向信使RNA，将与HCC发生发展相关的基因进行汇总，并按频率进行分类。最终在基因本体分析和京都基因和基因组途径百科全书中分析所选择的靶基因。miR-198在肝癌组织中的表达明显低于癌旁肝组织（1.30± 0.72vs2.01 ±0.58，P<0.001）。miR-198的低表达也与丙型肝炎病毒感染相关（r=-0.48，P<0.001），肿瘤包膜浸润（r=-0.43，P<0.001），转移（r=-0.26，P<0.010），肿瘤结节数（r=-0.25，P=0.013）、血管浸润（r=-0.24，P=0.017）和临床肿瘤淋巴结转移分期（r=-0.23，P=0.024）。通过至少四个数据库的并行预测，总共获得了1，048个基因，自然语言处理表明HCC有1，800个基因。此外，对127个重叠靶点进一步进行通路分析。miR-198潜在靶信使RNA中最丰富的Gene Ontology术语是生物学过程中的细胞运动、细胞迁移、细胞运动和细胞增殖调控;细胞成分中的细胞器腔、膜封闭腔和核腔;分子功能中的酶结合、蛋白结构域特异性结合和蛋白激酶活性。京都基因百科全书和基因组分析表明，这些靶基因明显参与了癌症中的粘着斑和通路。miR-198的低表达与HCC患者的几个临床病理参数相关。miR-198可能通过其靶基因在HCC的发生发展中发挥调控作用。
To investigate the clinicopathological value and potential roles of microRNA-198 (miR-198) in hepatocellular carcinoma (HCC). Ninety-five formalin-fixed paraffin-embedded HCC and the para-cancerous liver tissues were gathered. Real-time reverse transcription quantitative polymerase chain reaction was applied to determine the miR-198 expression. The association between the miR-198 expression and clinicopathological features was examined. Meanwhile, potential target messenger RNAs of miR-198 in HCC were obtained from 14 miRNA prediction databases and natural language processing method, in which we pooled the genes related to the tumorigenesis and progression of HCC and classified them by their frequency. The selected target genes were finally analyzed in the Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway. miR-198 expression was significantly lower in HCC than that in adjacent noncancerous liver tissues (1.30±0.72 vs 2.01±0.58, P<0.001). Low miR-198 expression was also correlated to hepatitis C virus infection (r=−0.48, P<0.001), tumor capsular infiltration (r=−0.43, P<0.001), metastasis (r=−0.26, P<0.010), number of tumor nodes (r=−0.25, P=0.013), vaso-invasion (r=−0.24, P=0.017), and clinical tumor node metastasis stage (r=−0.23, P=0.024). Altogether, 1,048 genes were achieved by the concurrent prediction from at least four databases and natural language processing indicated 1,800 genes for HCC. Further, 127 overlapping targets were further proceeded with for pathway analysis. The most enriched Gene Ontology terms in the potential target messenger RNAs of miR-198 were cell motion, cell migration, cell motility, and regulation of cell proliferation in biological process; organelle lumen, membrane-enclosed lumen, and nuclear lumen in cellular component; and enzyme binding, protein domain-specific binding, and protein kinase activity in molecular function. Kyoto Encyclopedia of Genes and Genomes analysis showed that these target genes were obviously involved in focal adhesion and pathways in cancer. Lower expression of miR-198 was related to several clinicopathological parameters in HCC patients. miR-198 might play a regulatory role through its target genes in the development of HCC.