Down-regulation of EDAG expression by retrovirus-mediated small interfering RNA inhibits the growth and IL-8 production of leukemia cells.
Embryonic development associated gene (EDAG), which is overexpressed in hematopoietic neoplasms and leukemia cell lines, has been reported to participate in the leukemia cell differentiation and proliferation. This study investigated whether retrovirus-mediated transfer of a siRNA against EDAG can reduce the growth of leukemia cells which highly express EDAG in vitro and in vivo. The stable transfected cells were identified with RT-PCR, the effect of EDAG/siRNA on the growth of the human erythroleukemia cell line HEL was analyzed by MTT assay, and angiogenic factor IL-8 release was evaluated by ELISA and RT-PCR. The results showed that EDAG/siRNA can silence the expression of EDAG in HEL cells. Down-regulation of EDAG expression by retrovirus-mediated siRNA inhibited the cell proliferation and tumor growth. Knockdown of EDAG expression by siRNA is also associated with decreased expression of the anti-angiogenic factor IL-8, suggesting that EDAG stimulates tumor growth at least in part by regulating angiogenesis. This study suggests that siRNA-mediated gene silencing of EDAG could potentially be a therapeutic strategy for EDAG over-expressing leukemia cells.
Anhui Province Key Laboratory of Molecular Medicine, Anhui Provincial Hospital Affiliated to Anhui Medical University, Hefei City, PR China. lingbin.ling@gmail.com
Bin
B
Ling
Ying
Y
Zhou
Dingqing
D
Feng
Guodong
G
Shen
Ting
T
Gao
Yongyun
Y
Shi
Haiming
H
Wei
Zhigang
Z
Tian
D001483:Base Sequence; D002455:Cell Division; D045744:Cell Line, Tumor; D002874:Chromosome Mapping; D002899:Chromosomes, Human, Pair 9; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics*; D007700:Kinetics; D004915:Leukemia, Erythroblastic, Acute / Q000235:genetics* / Q000473:pathology*; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics*; D034741:RNA, Small Interfering / Q000187:drug effects / Q000235:genetics*; D012190:Retroviridae / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014162:Transfection
C435745:HEMGN protein, human; D016209:Interleukin-8; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D013755:Tetradecanoylphorbol Acetate