Calcitriol increases Dicer expression and modifies the microRNAs signature in SiHa cervical cancer cells
Calcitriol increases Dicer expression and modifies the microRNAs signature in SiHa cervical cancer cells
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DOI：
10.1139/bcb-2015-0010
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发表时间：
2015-08-01
影响因子：
2.9
通讯作者：
Avila, Euclides
中科院分区：
文献类型：
--
作者：
Jose Gonzalez-Duarte, Ramiro;Cazares-Ordonez, Verna;Avila, Euclides
microRNA在癌症生物学中发挥重要作用。维生素D-3的激素形式骨化三醇调节肿瘤细胞中microRNA的表达。在本研究中，我们询问了骨化三醇是否会改变骨化三醇反应性宫颈癌细胞中microRNA加工机制的一些组分，即Drosha和Dicer。我们发现，骨化三醇治疗不影响Drosha mRNA，但它显着增加Dicer mRNA和蛋白质的表达在VDR阳性SiHa和HeLa细胞。在VDR阴性的C33-A细胞中，骨化三醇对Dicer mRNA没有影响。我们还在Dicer启动子中发现了维生素D反应元件，其在体外与维生素D和类维生素A X受体相互作用。为了探索这些结果的生物学可接受性，我们询问骨化三醇是否改变SiHa细胞中的microRNA表达谱。我们的研究结果表明，骨化三醇调节一组microRNA的表达，这些microRNA在癌症通路中具有潜在的调节功能，如miR-22，miR-296- 3 p和miR-498，它们发挥肿瘤抑制作用。总之，数据表明，在SiHa细胞中，骨化三醇可能通过位于其启动子中的维生素D反应元件刺激Dicer的表达。这可以解释其靶mRNA与抗癌途径相关的microRNA的骨化三醇依赖性调节，进一步增加了骨化三醇的各种抗癌机制。
MicroRNAs play important roles in cancer biology. Calcitriol, the hormonal form of vitamin D-3, regulates microRNAs expression in tumor cells. In the present study we asked if calcitriol would modify some of the components of the microRNA processing machinery, namely, Drosha and Dicer, in calcitriol-responsive cervical cancer cells. We found that calcitriol treatment did not affect Drosha mRNA; however, it significantly increased Dicer mRNA and protein expression in VDR-positive SiHa and HeLa cells. In VDR-negative C33-A cells, calcitriol had no effect on Dicer mRNA. We also found a vitamin D response element in Dicer promoter that interacts in vitro to vitamin D and retinoid X receptors. To explore the biological plausibility of these results, we asked if calcitriol alters the microRNA expression profile in SiHa cells. Our results revealed that calcitriol regulates the expression of a subset of microRNAs with potential regulatory functions in cancer pathways, such as miR-22, miR-296-3p, and miR-498, which exert tumor-suppressive effects. In summary, the data indicate that in SiHa cells, calcitriol stimulates the expression of Dicer possibly through the vitamin D response element located in its promoter. This may explain the calcitriol-dependent modulation of microRNAs whose target mRNAs are related to anticancer pathways, further adding to the various anticancer mechanisms of calcitriol.