Basic—Liver, Pancreas, and Biliary TractThe MicroRNA miR-139 Suppresses Metastasis and Progression of Hepatocellular Carcinoma by Down-regulating Rho-Kinase 2
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Cell Lines and Human Samples
Human HCC cell lines SMMC-7721 and BEL7402 were from the Shanghai Institute of Cell Biology, MHCC97L was from Fudan University (Dr Z. Y. Tang, Shanghai, China), and the LO2 cell line was from the Shanghai Cancer Institute (Dr J. R. Gu, Shanghai, China). Human HCC and their corresponding nontumorous liver samples were collected at the time of surgical resection at Queen Mary Hospital, The University of Hong Kong, from 1991 to 2008. Normal liver samples were collected from patients who had
miRNA Dysregulation in Human HCCs
To investigate the roles of miRNA in hepatocarcinogenesis, we first examined the miRNA expression profiles with TaqMan Human MicroRNA Low-Density Array on 4 microdissected primary HCCs and their corresponding nontumorous livers. Among the 666 unique miRNA probes, 315 (47%) miRNAs were expressed and detected in more than 50% of our samples. After normalization with the endogenous control U6, we found that 44 miRNAs were underexpressed in HCCs (T) as compared with their corresponding nontumorous
Discussion
Accumulation of aberrant gene expression is implicated in the progression of hepatocarcinogenesis. It has been reported that systemic delivery of tumor-suppressive miRNAs by adeno-associated virus in mice could efficiently inhibit HCC cell proliferation and progression without causing toxicity.4 Modulation of antimetastatic miRNA expression may serve as an attractive approach for treatment of advanced HCCs. To this end, we investigated the miRNA expression profiles of HCC patients and
Acknowledgments
The authors wish to thank Dr K. H. Kok from the Department of Biochemistry, The University of Hong Kong, for his valuable advice and discussion, and Dr Terence K. W. Lee from the Department of Pathology, The University of Hong Kong, for his expertise in lentiviral transduction.
C.C.-L.W. and C.-M.W. contributed equally to this work.
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Conflicts of interest The authors disclose the following: Irene Oi-Lin Ng has received a Research Collaborative Grant from Pfizer, Inc. The remaining authors disclose no conflicts.
Funding This study was supported by the Hong Kong Research Grants Council Collaborative Research Fund (HKU 1/06C and HKU 7/CRG/09); Irene Oi-Lin Ng is a Loke Yew Professor in Pathology.