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Lower expressed miR-198 and its potential targets in hepatocellular carcinoma: a clinicopathological and in silico study

Authors Huang W, Wang H, Yang H, Ren F, Luo Y, Huang C, Liang Y, Liang H, Chen G, Dang Y

Received 19 March 2016

Accepted for publication 30 June 2016

Published 22 August 2016 Volume 2016:9 Pages 5163—5180

DOI https://doi.org/10.2147/OTT.S108828

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Ram Prasad

Peer reviewer comments 4

Editor who approved publication: Dr Jianmin Xu


Wen-Ting Huang,1,* Han-Lin Wang,1,* Hong Yang,2 Fang-Hui Ren,1 Yi-Huan Luo,1 Chun-Qin Huang,1 Yue-Ya Liang,1 Hai-Wei Liang,1 Gang Chen,1 Yi-Wu Dang1

1Department of Pathology, 2Department of Ultrasonography, First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China

*These authors contributed equally to this work

Purpose: To investigate the clinicopathological value and potential roles of microRNA-198 (miR-198) in hepatocellular carcinoma (HCC).
Methods: 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.
Results: 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.
Conclusion: 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.

Keywords: miR-198, hepatocellular carcinoma, metastasis, RT-qPCR, in silico

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