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类固醇激素骨化三醇及其类似物他卡西醇可抑制人乳腺癌MCF-7细胞系中miR-125b的表达。

Steroid hormone calcitriol and its analog tacalcitol inhibit miR-125b expression in a human breast cancer MCF-7 cell line.

作者信息

Klopotowska Dagmara, Matuszyk Janusz, Wietrzyk Joanna

机构信息

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.

出版信息

Steroids. 2019 Jan;141:70-75. doi: 10.1016/j.steroids.2018.11.014. Epub 2018 Nov 29.

Abstract

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.

摘要

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。

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