title: RUNX3 inhibits survivin expression and induces cell apoptosis in gastric cancer.
abstract: Transcription factor RUNX3 is associated with gastric tumorigenesis and progression through regulating the expression of its target genes. Survivin is a member of the inhibitor of apoptosis (IAP) family and has been shown to inhibit cell apoptosis and promote cell proliferation. Increased survivin expression has been found in various cancer types, including gastric cancer. In this study, we found that restoration of RUNX3 promotes cell apoptosis through inhibiting the survivin expression, while RUNX3 inhibition increases the expression of survivin in gastric cancer cell lines. Moreover, RUNX3 over-expression inhibits,whereas its inhibition increases, the promoter activity of survivin gene, respectively. RUNX3-R122C, a mutation located in the conserved Runt domain, has no effect on the promoter activity of survivin gene. We further identified a RUNX3-binding site in the promoter of survivin gene and the binding of RUNX3 on survivin promoter leads to significantly inhibition of survivin expression. Finally, we confirmed the negative correlation of RUNX3 and survivin expression in clinical specimens of gastric cancer. These findings reveal a novel mechanism of RUNX3 for the induction of cell apoptosis in human gastric cancer.
authors.affiliation: Department of Biochemistry and molecular biology, School of Medicine, Shandong University, Jinan, PR China.
authors.forename: Zhifang
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Biochemistry and molecular biology, School of Medicine, Shandong University, Jinan, PR China.
authors.forename: Xinchao
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry and molecular biology, School of Medicine, Shandong University, Jinan, PR China.
authors.forename: Xia
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Biochemistry and molecular biology, School of Medicine, Shandong University, Jinan, PR China.
authors.forename: Long
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Microbiology and Key Laboratory for Experimental Teratology of Chinese Ministry of Education, School of Medicine, Shandong University, Jinan, PR China.
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Microbiology and Key Laboratory for Experimental Teratology of Chinese Ministry of Education, School of Medicine, Shandong University, Jinan, PR China.
authors.forename: Han
authors.initials: H
authors.lastname: Yu
authors.affiliation: Department of Microbiology and Key Laboratory for Experimental Teratology of Chinese Ministry of Education, School of Medicine, Shandong University, Jinan, PR China.
authors.forename: Yundong
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Biochemistry and molecular biology, School of Medicine, Shandong University, Jinan, PR China.
authors.forename: Jiping
authors.initials: J
authors.lastname: Zeng
authors.affiliation: Department of Microbiology and Key Laboratory for Experimental Teratology of Chinese Ministry of Education, School of Medicine, Shandong University, Jinan, PR China. Electronic address: jiajihui@sdu.edu.cn.
authors.forename: Jihui
authors.initials: J
authors.lastname: Jia
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000502:physiology*; D045744:Cell Line, Tumor; D050677:Core Binding Factor Alpha 3 Subunit / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology; D000077022:Survivin; D014158:Transcription, Genetic
chemical_list: C107489:BIRC5 protein, human; D050677:Core Binding Factor Alpha 3 Subunit; D051034:Inhibitor of Apoptosis Proteins; C493729:Runx3 protein, human; D000077022:Survivin
keywords: Cell apoptosis; Gastric cancer; RUNX3; Survivin