Association of Casp3 microRNA Target Site (1049216) SNP With the Risk and Progress of Cervical Squamous Cell Carcinoma.

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.

• Authors: Xin Guo, Zhiming Dong, Sohsuke Yamada, Yuanyuan Li, Yanli Guo, Supeng Shen, Jia Liang, Akihide Tanimoto, Wei Guo
• Journal: International journal of gynecological cancer : official journal of the International Gynecological Cancer Society (Int J Gynecol Cancer) Vol. 27 Issue 2 Pg. 206-213 (02 2017) ISSN: 1525-1438 [Electronic] England
• PMID: 28114230 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA, Neoplasm
• CASP3 protein, human
• Caspase 3

Topics

• Adult
• Carcinoma, Squamous Cell (blood, enzymology, genetics)
• Case-Control Studies
• Caspase 3 (biosynthesis, genetics)
• Cell Line, Tumor
• DNA, Neoplasm (blood, genetics)
• Female
• HeLa Cells
• Humans
• Middle Aged
• Polymerase Chain Reaction
• Polymorphism, Restriction Fragment Length
• Polymorphism, Single Nucleotide
• Transfection
• Uterine Cervical Neoplasms (blood, enzymology, genetics)