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• Miao, R
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• Zhao, H
• Zhong, Y
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• Miao, R
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• Robson, SC.
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• Zhao, H
• Zhong, Y
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• Miao, R
• Li, G
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Int. J. Mol. Sci. 2013, 14(1), 1105-1118; doi:10.3390/ijms14011105

Article

Identification of Recurrence Related microRNAs in Hepatocellular Carcinoma after Surgical Resection

Zhen Yang ^1,2,3,† , Ruoyu Miao ^4,† , Guangbing Li ^1,5 , Yan Wu ⁶ , Simon C. Robson ⁶ , Xiaobo Yang ¹ , Yi Zhao ⁴ , Haitao Zhao ^1,*  and Yang Zhong ^3,7,*

¹ Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing 100730, China ² Institute of Biomedical Sciences, Fudan University, Shanghai 200433, China ³ School of Life Science, Fudan University, Shanghai 200032, China ⁴ Bioinformatics Research Group, Center for Advanced Computing Technology Research, Institute of Computing Technology, Chinese Academy of Sciences, Beijing 100190, China ⁵ Department of Liver Transplantation and Hepatobiliary Surgery, Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, China ⁶ Liver Center and Transplant Institute, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard University, Boston, MA 02215, USA ⁷ Institute of Biodiversity Science and Geobiology, Tibet University, Lhasa 850000, China ^† These authors contributed equally to this work.

* Authors to whom correspondence should be addressed.

Received: 31 October 2012; in revised form: 11 December 2012 / Accepted: 24 December 2012 / Published: 8 January 2013

(This article belongs to the Special Issue Non-Coding RNAs 2012)

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Abstract: Hepatocellular carcinoma (HCC) is one of the most aggressive human cancers with a high frequency of post-surgical recurrence. It is very critical to diagnose HCC recurrence at an early stage for a better therapeutic treatment. In this study, we examined the microRNA (miRNA) expression profiling in tumor tissues obtained from early and late recurrent HCC patients post-resection, using a microarray assay. A total of 32 miRNAs were identified to be differentially expressed during the progression of recurrence. Among these, 16 miRNAs were upregulated and 16 were downregulated. In addition, this miRNA expression signature was further validated by quantitative real-time polymerase chain reaction (qRT-PCR) analysis. Moreover, functional annotation of predicted target genes of these recurrent HCC-related miRNAs indicates that multiple biological pathways (i.e., focal adhesion pathway, cancer-related pathways and mitogen-activated protein kinase (MAPK) signaling) that are all critical for cancer development and progression, may participate in the recurrence of HCC. Our data suggest potential molecular mechanisms underpinning miRNA-controlled HCC recurrence, and support the notion that miRNA expression signature and miRNA-based therapy can be useful tools for a better diagnosis and treatment stratification of this disease.

Keywords: microRNA; expression; hepatocellular carcinoma; recurrence

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