Upregulation of Dicer expression by calcitriol induces microRNAs with potential tumor-suppressive effects in cancer cervical cells

Dicer is a key endoribonuclease of the microRNA biogenetic machinery. Downregulation of Dicer has been associated with aberrant expression of microRNAs and the promotion of tumorigenesis. Calcitriol, the hormonal form of vitamin D3, increases microRNA expression in tumor cells, but the mechanism is not yet understood. Given the essential role of Dicer in microRNAs biogenesis, the purpose of this study was to evaluate whether this gene is a target for calcitriol and to explore the effects of this hormone on microRNA expression. Our findings demonstrate that calcitriol increased Dicer mRNA and protein in SiHa and HeLa cervical cancer cells, which expressed the vitamin D receptor. The inductive effect of calcitriol on Dicer mRNA was not observed in C33-A cells lacking this nuclear receptor. To explore the potential effect of Dicer upregulation by calcitriol on microRNA processing, we performed a microRNA profiling study in SiHa cells treated with calcitriol. The analysis of microRNA expression revealed that this hormone promotes the maturation of a subset of microRNAs with potential regulatory function in cancer pathways. Among these, miR-22 and miR-296-3p have already been associated with tumor-supressive effects. Our results suggest that Dicer upregulation by calcitriol could be associated, at least in part, with an increase in the maturation of a subset of tumor-suppressor microRNAs in cervical cancer cells. SiHa cell lines were treated with calcitriol or ethanol as vehicle for 24 or 48 h in medium supplemented with charcoal-treated serum.