Background and purpose: Sterile alpha motif and histidine/aspartic acid domain-containing protein 1 (SAMHD1) is found to inhibit cell g

rowth 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.