Abstract: Objective To investigate the impact of 5-fluorouracil (5-FU) on miR-22 expression in human hepatocellular carcinoma (HCC) cell lines and to elucidate the molecular mechanism of 5-fluorouracil for HCC chemotherapy. Methods Real-time PCR analysis was conducted to determine the expression levels of miR-22 in HCC tissue specimens and HCC cell lines. The expression of miR-22 and pri-miR-22 （primary miR-22） was evaluated in HepG2 and Huh7 cells with 5-FU treatment by using real-time PCR and we also performed Western blot analysis to detect the protein levels of HDAC4 in HCC cells with the same treatment. A rescue assay was employed by using 5-FU treatment in combination with miR-22 inhibitor (Anti-22) to further investigate the correlation among 5-FU, miR-22, and HCC cell growth. Results miR-22 expression depicted a significant downregulation in HCC tissues and cell lines (P<0.01). 5-FU treatment led to an augment of miR-22 expression in HepG2 and Huh7 cells (P<0.001) and resulted in a decrease of HDAC4 protein levels, which was verified as a direct target of miR-22 in HCC cells (P<0.01). Conclusion 5-FU represents its suppressive effect on HCC growth at least partly via miR-22-mediated HDAC4 axis.

Key words: miR-22, 5-Fluorouracil, HCC, chemotherapy