Low folate levels are associated with methylation-mediated transcriptional repression of miR-203 and miR-375 during cervical carcinogenesis

Abstract

The aim of the present study was to investigate the correlation between a lack of folic acid and the abnormal expression of microRNA (miR)-203 and miR-375 in cervical cancer. In total, 60 tissue samples of cervical intraepithelial neoplasia (CIN) or stage IA‑IIA cervical cancer (study group), and 30 samples without soluble interleukin or malignancy (control group) were examined. The expression of miR‑203 and miR‑375 was detected using reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR), and the difference in expression levels was quantified using the 2‑ΔΔCq method. In addition, CaSki cervical cancer cells were cultured in vitro and treated with various concentrations of folic acid. The DNA methylation states of miR‑203 and miR‑375 were subsequently detected by methylation‑specific PCR, and the expression levels were evaluated using RT‑PCR. miR‑203 and miR‑375 were significantly downregulated in CIN and cervical cancer tissues, compared with the control group. There was a marked difference in terms of the expression levels of miR‑375 between the two groups (P<0.05). In CaSki cells, as the concentration of folic acid increased, the positive rate of DNA methylation of miR‑203 and miR‑375 decreased, while the expression levels of miR‑203 and miR‑375 demonstrated a gradual increase, which indicated that the latter two parameters were negatively correlated (P<0.05). Compared with normal cervical tissue, the expression levels of miR‑203 and miR‑375 were downregulated in CIN and cervical cancer. Methylation of these two miRs was apparent in CaSki cells, and was associated with a lack of folic acid. Therefore, reduced levels of folic acid, leading to increased methylation of miR‑203 and miR-375, may be significant events during cervical carcinogenesis.