Objective        To determine the differential expression profile between apurinic/apyrimidinic endonuclease (APE1) knockdown HOS cells and wild-type HOS cells

and to investigate the roles of these differential miRNAs in osteosarcoma cells.       Methods       After APE1 expression were down-regulated by APE1-siRNA adenovirus Ad5/F35-APE1 siRNA in HOS cells

microarray were used to confirm the change of microRNAs (miRNAs) in APE1-knockdown osteosarcoma HOS cells and wide-type cells. The results were confirmed by qRT-PCR. Comprehensive bioinformatics-based analysis

including target genes

gene ontology (GO) analysis and pathway analysis were carried out to analyze these differential expressed miRNAs and their functions.       Results        miRNA microarray indicated that there were 32 miRNAs differentially expressed in APE1 knockdown HOS cells. qRT-PCR demonstrated that 13 miRNAs (coincidence with the results of microarray) were significantly changed (2-fold)

with 7 of them up-regulated and the other 6 down-regulated. Furthermore

GO analysis showed that these miRNAs and their target genes affected by APE1 expression were located in intra-cellular and played roles in the protein and DNA binding

transcription

developmental process and cellular metabolism. Pathway analysis showed that these miRNAs targets were involved in adhere junction

axon guidance

ECM-receptor interaction

cancer pathway

as well as some key cell signaling pathways (such as TGF-β

MAPK

EtbB

Wnt

mTOR and p53 signaling pathway).       Conclusion        APE1 appears to have a direct effect on global miRNAs expression. Bioinformatics-based analysis indicated APE1 may regulate miRNAs to affect the expression of downstream target genes. These interactions may be involved in the tumor

progenesis

cell survival

proliferation and adhesion

and many cell signal pathways

especially with regard to the tumorigenesis

development

invasion and metastasis of osteosarcoma.