title: Association of Casp3 microRNA Target Site (1049216) SNP With the Risk and Progress of Cervical Squamous Cell Carcinoma.
abstract: In the present study, we investigated the relationship between the single-nucleotide polymorphism (SNP) of caspase-3 rs1049216 (C > T), a miRNA target site, and the risk and progression of cervical cancer.
  
  
  
  Using polymerase chain reaction-restriction fragment length polymorphism, we evaluated the genotype and distribution of caspase-3 rs1049216 in 515 patients with cervical squamous cell cancer and 415 controls. In additional experiments, we transfected luciferase reporter plasmids carrying T or C allele and/or miRNA mimics into the human cervical cell lines (HeLa and C-33A) to analyze its roles in the regulation of caspase-3 expression. By immunohistochemistry, the protein level of caspase-3 expression was examined in tumor tissues from 515 patients with cervical squamous cell cancer.
  
  
  
  We found that the TT genotype of caspase-3 rs1049216 conferred a significantly decreased risk of cervical cancer (adjusted odds ratio, 0.35; 95% confidence interval, 0.154-0.581) and may be associated with the progression of this cancer. Although the expression of caspase-3 in the TT genotype was higher than that in CC/CT genotype in peripheral blood mononuclear cells and tumor tissues. Additional luciferase analysis showed that the rs1049216 variant T allele was associated with significantly higher luciferase activity, compared with the C allele in the transfected cells, and when cotransfected with miRNAs, miRNA-181a could downregulate the luciferase activity in the cells that transfected the construct containing C allele, compared with T allele, which had not happened in the presence of other miRNAs selected.
  
  
  
  These data indicate that through upregulating the expression of caspase-3, the TT genotype of caspase-3 rs1049216 can be associated with not only the risk of cervical cancer but also the progression of this cancer.
authors.affiliation: *Laboratory of Pathology, Hebei Cancer Institute, the Fourth Hospital of Hebei Medical University, Hebei, China; †Department of Molecular and Cellular Pathology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan; and ‡Physical Examination Center, Hebei People's Hospital, Hebei, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Guo
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Dong
authors.forename: Sohsuke
authors.initials: S
authors.lastname: Yamada
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Li
authors.forename: Yanli
authors.initials: Y
authors.lastname: Guo
authors.forename: Supeng
authors.initials: S
authors.lastname: Shen
authors.forename: Jia
authors.initials: J
authors.lastname: Liang
authors.forename: Akihide
authors.initials: A
authors.lastname: Tanimoto
authors.forename: Wei
authors.initials: W
authors.lastname: Guo
mesh_terms: D000328:Adult; D002294:Carcinoma, Squamous Cell / Q000097:blood / Q000201:enzymology / Q000235:genetics*; D016022:Case-Control Studies; D053148:Caspase 3 / Q000096:biosynthesis / Q000235:genetics*; D045744:Cell Line, Tumor; D004273:DNA, Neoplasm / Q000097:blood / Q000235:genetics; D005260:Female; D006367:HeLa Cells; D006801:Humans; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D014162:Transfection; D002583:Uterine Cervical Neoplasms / Q000097:blood / Q000201:enzymology / Q000235:genetics*
chemical_list: D004273:DNA, Neoplasm; C505407:CASP3 protein, human; D053148:Caspase 3