Klopotowska Dagmara, Matuszyk Janusz, Wietrzyk Joanna
Laboratory of Experimental Anticancer Therapy, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 12 R. Weigla Street, 53-114 Wroclaw, Poland.
Laboratory of Signal Transduction Molecules, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 12 R. Weigla Street, 53-114 Wroclaw, Poland.
Steroids. 2019 Jan;141:70-75. doi: 10.1016/j.steroids.2018.11.014. Epub 2018 Nov 29.
MiR-125b belongs to the class of microRNAs, which are short endogenous non-coding RNAs that negatively regulate gene expression at the post-transcriptional level. Recently, it was reported that miR-125b was found to promote migration and invasion of MCF-7 cells and was involved in chemotherapeutic resistance. Decreasing miR-125b expression would have potential therapeutic significance in preventing dissemination of breast cancer cells. The objective of this study was to evaluate miR-125b expression levels in MCF-7 cells following treatment with 1,25-dihydroxyvitamin D (calcitriol) and 1,24-dihydroxyvitamin D (tacalcitol), active metabolite and synthetic analog of vitamin D, respectively. We found that treatment with both calcitriol and tacalcitol caused a decrease in miR-125b expression. In addition, treatment with calcitriol and tacalcitol resulted in an increase in the level of pro-apoptotic BAK1 protein encoded by the target gene of miR-125b. We are discussing the putative mechanism of inhibition of the miR-125b expression by vitamin D receptor (VDR) agonists and we suggest that calcitriol and tacalcitol may be used as a miR-125b inhibitor in breast cancer cells expressing VDR.
微小RNA-125b(MiR-125b)属于微小RNA类别,微小RNA是短链内源性非编码RNA,可在转录后水平负向调控基因表达。最近有报道称,发现MiR-125b可促进MCF-7细胞的迁移和侵袭,并参与化疗耐药。降低MiR-125b的表达在预防乳腺癌细胞扩散方面可能具有潜在的治疗意义。本研究的目的是评估分别用维生素D的活性代谢物1,25-二羟基维生素D(骨化三醇)和合成类似物1,24-二羟基维生素D(他骨化醇)处理MCF-7细胞后MiR-125b的表达水平。我们发现,骨化三醇和他骨化醇处理均导致MiR-125b表达降低。此外,骨化三醇和他骨化醇处理导致MiR-125b靶基因编码的促凋亡BAK1蛋白水平升高。我们正在探讨维生素D受体(VDR)激动剂抑制MiR-125b表达的假定机制,并建议骨化三醇和他骨化醇可作为表达VDR的乳腺癌细胞中MiR-125b的抑制剂。