Abstract: Background and purpose: Sterile alpha motif and histidine/aspartic acid domain-containing protein 1 (SAMHD1) is found to inhibit cell growth in a variety of tumor cells, however, whether it influences the growth of hepatocellular carcinoma (HCC) cells is unclear. This study aimed to investigate the effect of SAMHD1 on the proliferation, apoptosis and cell cycle of Huh7 cells by regulating the expression of p27. Methods: The expressions of SAMHD1 in normal hepatocytes and different types of HCC cells were detected by Western blot. Recombinant plasmids of overexpression SAMHD1, dNTPase mutants (SAMHD1-D207N) and phosphorylation mutant (SAMHD1-T592E) were constructed by gene recombination technology. The effects of overexpression of SAMHD1, D207N and T592E mutants or silencing the expression of SAMHD1 by siRNA on the cells proliferation were employed by methyl thiazolyl tetrazolium (MTT) assay, and the effects on the cell cycle and apoptosis of cells were measured by flow cytometry. Results: The expression of SAMHD1 was significantly increased in HCC cells. Overexpression of SAMHD1, SAMHD1-D207N and SAMHD1-T592E inhibited the proliferation of Huh7 cells, and induced cell cycle arresting in G ₁ /G ₀ phase. Converse results were obtained by silencing the overexpression of SAMHD1. Mechanism studies indicated that SAMHD1 could up-regulate the expression of cyclin-dependent kinase inhibitor p27. Moreover, the mRNA expression of p27 was positively correlated with the expression of SAMHD1 in HCC samples derived from The Cancer Genome Atlas (TCGA) database. Conclusion: Overexpression of SAMHD1 can lead to an increase in the expression of p27, resulting in the cell cycle arrest in G ₁ /G ₀ phase, and inhibits the proliferation of HCC cells, which is independent of dNTPase activity and phosphorylation.

Key words: Hepatocellular carcinoma, Sterile alpha motif and histidine/aspartic acid domain-containing protein 1, Proliferation, p27