title: Folate deficiency and aberrant expression of DNA methyltransferase 1 were associated with cervical cancerization.
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.
authors.forename: Jin-tao
authors.initials: JT
authors.lastname: Wang
authors.forename: Ling
authors.initials: L
authors.lastname: Ding
authors.forename: Shi-Wen
authors.initials: SW
authors.lastname: Jiang
authors.forename: Junxia
authors.initials: J
authors.lastname: Hao
authors.forename: Wei-min
authors.initials: WM
authors.lastname: Zhao
authors.forename: Quin
authors.initials: Q
authors.lastname: Zhou
authors.forename: Zuo-kai
authors.initials: ZK
authors.lastname: Yang
authors.affiliation: Department of Epidemiology, School of Public Health, Shanxi Medical University, Taiyuan 030001, China. wangjt59@163.com.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000209:etiology / Q000235:genetics / Q000473:pathology*; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics*; D019175:DNA Methylation; D005260:Female; D005492:Folic Acid / Q000097:blood; D005494:Folic Acid Deficiency / Q000150:complications*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D012720:Severity of Illness Index; D002583:Uterine Cervical Neoplasms / Q000209:etiology / Q000235:genetics / Q000473:pathology*; D002578:Uterine Cervical Dysplasia / Q000209:etiology / Q000235:genetics / Q000473:pathology*
chemical_list: D012333:RNA, Messenger; D005492:Folic Acid; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000619380:DNMT1 protein, human