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Association of Casp3 microRNA Target Site (1049216) SNP With the Risk and Progress of Cervical Squamous Cell Carcinoma
  1. Xin Guo, PhD,
  2. Zhiming Dong, PhD,
  3. Sohsuke Yamada, PhD,
  4. Yuanyuan Li, MS,
  5. Yanli Guo, PhD,
  6. Supeng Shen, MS,
  7. Jia Liang, MS,
  8. Akihide Tanimoto, PhD and
  9. Wei Guo, PhD
  1. * Laboratory of Pathology, Hebei Cancer Institute, the Fourth Hospital of Hebei Medical University, Hebei, China;
  2. Department of Molecular and Cellular Pathology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan; and
  3. Physical Examination Center, Hebei People's Hospital, Hebei, China.
  1. Address correspondence and reprint requests to Wei Guo, PhD, Laboratory of Pathology, Hebei Cancer Institute, the Fourth Hospital of Hebei Medical University, Jiankang Rd 12, Shijiazhuang 050011, Hebei, China. E-mail: guowei7303{at}163.com.

Abstract

Objective 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.

Materials and Methods 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.

Results 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.

Conclusions 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.

  • Caspase 3
  • miRNA
  • Single nucleotide polymorphism
  • Apoptosis
  • Cervical squamous cell carcinoma

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Footnotes

  • The authors declare no conflicts of interest.

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