Folate inhibits miR-27a-3p expression during cervical carcinoma progression and oncogenic activity in human cervical cancer cells

Abstract

BackgroundFolate deficiency has been long implicated in cancer development. Although the role of folate in preventing cervical cancer is still unclear, emerging evidence shows that microRNAs (miRs) have great influence on tumor cell migration and invasion. ObjectivesThe purpose of this study was to conduct an integrated analysis of miR expression in squamous cell carcinoma tissues with adequate or deficient serum folate. Further, study conducted tissue validation and functional analysis of miRs to uncover novel pathogenic mechanisms on the role of folate in squamous cell carcinoma (SCC). Materials and methodsmiR expression profiles were obtained from five paired primary SCC tumors with sufficient or deficient serum folate levels through Affymetrix GeneChip microRNA 4.0. This was followed by an integrated bioinformatics analysis and expanded sample size to verify core miRs by molecular biological validation. HeLa and SiHa cells with different concentrations of folate were used to clarify the roles of miR-27a on cell proliferation, migration, and invasion. MiR-27a expression was measured by the quantitative real-time polymerase chain reaction. Cell counting proliferation, wound healing, and transwell invasion assays were used to determine cell survival, proliferation, migration, and invasion abilities, respectively. ResultsOur study found increasing miR-27a expression in serum of normal, high-grade squamous intraepithelial lesion (HSIL), and SCC tissues (in order of magnitude), which trend was negatively correlated with serum folate content. Further, there were significant differences in cellular miR-27a expression between 200 nM and 500 nM folate concentrations, with higher folate concentrations showing lower proliferation, migration, and invasion in SCC. Finally, miR-27a promoted proliferation and invasion in HeLa cells, whereas a miR-27a inhibitor blocked cell proliferation and invasion. ConclusionThere is a significant association between miR-27a expression and folate during cervical carcinoma progression. Therefore, miR-27a could be used as a new biomarker for SCC diagnosis and prediction, suggesting a new therapeutic strategy for SCC treatment.