Title:Folate Deficiency and Aberrant Expression of DNA Methyltransferase 1 were Associated with Cervical Cancerization
Volume: 20
Issue: 11
Author(s): Wang Jin-tao, Ding Ling, Jiang Shi-Wen, Hao Junxia, Zhao Wei-min, Zhou Qin, Yang Zuo-kai and Zhang Li
Affiliation:
Keywords:
Folate, DNA methyltransferase 1 (DNMT1), Cervical cancerization, Cervical cancer cells.
Abstract: DNA methyltransferase 1 (DNMT1) plays a significant role in maintaining DNA methylation. Aberrant DNA methylation is a
recognized feature of human cancers and folate is directly involved in DNA methylation via one-carbon metabolism. Previous reports
also have suggested that folate deficiency was associated with many cancers. The aim of the present study was to evaluate the effect of
folate deficiency and aberrant expression of DNA methyltransferase 1 (DNMT1) on cervical cancerization. The expression of DNMT1
protein and mRNA and levels of serum folate were detected in 238 women with a diagnosis of normal cervix (NC，n = 53), cervical intraepithelial
neoplasia (CIN I, n = 52; CIN II/III, n = 53), and squamous cell carcinoma of the cervix (SCC; n = 80). In addition, the expression
of DNMT1 protein and mRNA was measured in cervical cancer cells (Caski and C33A) treated by different concentration of folate.
Serum folate levels decreased and expression levels of DNMT1 protein and mRNA increased gradually with progressive severity of
the cervix lesions (P<0.001). It was found that folate was able to reduce the viability of Caski or C33A cell (r=0.978, P=0.002; r=0.984,
P<0.001) and regulated aberrant expression of DNMT1 protein (r=-0.859, P=0.01; r=-0.914, P<0.001) and mRNA (r=-0.297, P=0.159;
r=0.433, P=0.034) in vitro. Our findings indicated that the low-level of serum folate and high-expression of DNMT1 protein or mRNA
was significantly associated with cervical carcinogenesis. Folate deficiency and aberrant expression of DNA methyltransferase 1 had additive
effect on cervical cancerization. Folate supplement and recovery of aberrant DNA methylation status may offer a new strategy for
prevention and therapy of cancers.
