As
a DNA repair
protein,
flap endonuclease 1 (FEN1), a structure-specific 5' nuclease, plays pivotal roles in the maturation of
Okazaki fragments, long-patch base excision repair, restarting of stalled replication forks and telomere maintenance. FEN1 possesses 5'
endonuclease,
5' exonuclease and gap-
endonuclease activities, which render it an essential node in maintaining genome fidelity. The aim of this study was to investigate the association between the expression level of FEN1 and
gastric cancer and to explore the role of FEN1 in
carcinogenesis and the progression of
gastric cancer. The
mRNA and
protein expression of FEN1 in 42 matched pairs of human gastric
tumor tissues and corresponding normal tissues were measured by semiquantitative reverse transcription-PCR and immunohistochemical staining. FEN1 expression was downregulated in the SGC-7901
gastric cancer cells following transfection with
siRNA targeting the FEN1 gene. Western blot analysis was used to evaluate the
protein expression of FEN1 in SGC-7901 human
gastric cancer cells in order to verify the transfection efficiency of FEN1
siRNA. Moreover, cell proliferation was analyzed by MTS assay. The apoptosis of the cells was determined by flow cytometry. Our results revealed that FEN1 was overexpressed in
gastric cancer in comparison to the corresponding normal gastric tissues (P<0.01). We further confirmed that FEN1 expression has a positive correlation with the degree of differentiation (P=0.027),
lymphatic metastasis (P=0.001),
tumor size (P=0.026) and TNM stage (P=0.020) of
gastric cancer. A high FEN1 expression in SGC-7901 cells can be effectively downregulated by
siRNA constructed to target the FEN1 gene. Moreover, the inhibition of FEN1 expression suppressed the proliferation and induced the apoptosis of SGC-7901 cells. Taken together, our results indicate that FEN1 may be a promising
biomarker for the diagnosis of
gastric cancer and individual
therapy.