Send to:

Choose Destination
See comment in PubMed Commons below
J Gastroenterol Hepatol. 2013 Mar;28(3):565-75. doi: 10.1111/j.1440-1746.2012.07271.x.

Involvement of microRNA-224 in cell proliferation, migration, invasion, and anti-apoptosis in hepatocellular carcinoma.

Author information

  • 1Department of Medicine and Molecular Science, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Sciences, Hiroshima City, Hiroshima, Japan.



Changes in microRNA (miRNA) expression have been detected in a broad range of biological processes including cancer. Here we determined the role of miRNA dysregulation in hepatocellular carcinoma (HCC).


We investigated the expression of nine cancer-related miRNAs in HCC. Among these, miR-224 was the most significantly uprgulated in HCC tissues (n = 18), compared with normal (n = 9) and HCC adjacent non-tumorous liver tissues (n = 18). After leading-in currently reported gene targets from Sanger miRBase, we characterized the expression profiles of target genes of miR-224 using cDNA microarray. The altered expression was subsequently validated by real-time polymerase chain reaction and Western blot. The phenotypic changes by miR-224 expression were identified by cell viability, apoptosis, and in vitro scratch assays.


The microarray analysis and miRNA target prediction analysis allowed the identification of significant changes in 68 putative gene targets after overexpression of miR-224. The high-ranking genes CDC42, CDH1, PAK2, BCL-2, and MAPK1 were confirmed as important targets of miR-224 and involvement in hepatocarcinogenesis. Overexpression of miR-224 significantly in Hek293 and Huh7 cells altered the expression levels of CDC42, CDH1, PAK2, and BCL-2 at both mRNA and protein levels. Similar changes in the expression of the same genes were also observed in HCC tissues. Via functional analyses, cell proliferation, migration and anti-apoptosis were proved to be affected by miR-224 expression.


The results suggest that miR-224 plays a role in cell proliferation, migration, invasion, and anti-apoptosis in HCC by directly binding to its gene targets, implicating this RNA in HCC development and progression.

© 2012 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Wiley
    Loading ...
    Write to the Help Desk