BACKGROUND: Recently, microRNAs in cancer development have attracted much 
attention, but their roles in tumorigenesis are still largely unknown. In this 
study, a functional role of miR-22 in hepatocellular carcinoma (HCC) development 
has been identified.
METHODS: Quantitative real-time PCR was used to determine the level of miR-22 
transcript in HCC clinical samples, and its correlation with disease-free 
survival was determined using Kaplan-Meier method. Restoration of miR-22 
expression was carried out in HCC cell lines to assess its influence on HCC cell 
proliferation and tumourigenicity.
RESULTS: In the 160 paired HCC tissue samples, miR-22 expression was 
downregulated in HCC, and low miR-22 expression in HCC was predictive of poor 
survival in HCC patients. Functional studies indicated that ectopic expression 
of miR-22 significantly inhibits HCC cell proliferation and tumourigenicity. 
Furthermore, histone deacetylase 4 (HDAC4), known to have critical roles in 
cancer development, was proved to be directly targeted and regulated by miR-22. 
Furthermore, HDAC4 was upregulated in miR-22-downregulated HCC tissues, 
suggesting that downregulation of miR-22 might participate in HCC carcinogenesis 
and progression through potentiation of HDAC4 expression. In addition, cell 
proliferation was also suppressed by knockdown of HDAC4 or treatment with HDAC 
inhibitor trichostatin A in HCC cell lines.
CONCLUSION: miR-22, downregulated in HCC, has an anti-proliferative effect on 
HCC cells both in vitro and in vivo. Furthermore, miR-22 may have considerable 
potential in identification of the prognosis and application of cancer therapy 
for HCC patients.