Daiwile Atul P, Sivanesan Saravanadevi, Izzotti Alberto, Bafana Amit, Naoghare Pravin K, Arrigo Patrizio, Purohit Hemant J, Parmar Devendra, Kannan Krishnamurthi
Environmental Health Division, National Environmental Engineering Research Institute (NEERI), CSIR, Nagpur 440020, India.
Department of Health Sciences, University of Genoa, No. 5, 16126 Genoa, Italy ; IRCCS AOU San Martino IST, No. 10, 16132 Genoa, Italy.
Biomed Res Int. 2015;2015:274852. doi: 10.1155/2015/274852. Epub 2015 Aug 3.
Fluorosis is caused by excess of fluoride intake over a long period of time. Aberrant change in the Runt-related transcription factor 2 (RUNX2) mediated signaling cascade is one of the decisive steps during the pathogenesis of fluorosis. Up to date, role of fluoride on the epigenetic alterations is not studied. In the present study, global expression profiling of short noncoding RNAs, in particular miRNAs and snoRNAs, was carried out in sodium fluoride (NaF) treated human osteosarcoma (HOS) cells to understand their possible role in the development of fluorosis. qPCR and in silico hybridization revealed that miR-124 and miR-155 can be directly involved in the transcriptional regulation of Runt-related transcription factor 2 (RUNX2) and receptor activator of nuclear factor κ-B ligand (RANKL) genes. Compared to control, C/D box analysis revealed marked elevation in the number of UG dinucleotides and D-box sequences in NaF exposed HOS cells. Herein, we report miR-124 and miR-155 as the new possible players involved in the development of fluorosis. We show that the alterations in UG dinucleotides and D-box sequences of snoRNAs could be due to NaF exposure.
氟中毒是由长期过量摄入氟化物引起的。与Runt相关的转录因子2(RUNX2)介导的信号级联异常变化是氟中毒发病机制中的决定性步骤之一。迄今为止,尚未研究氟化物对表观遗传改变的作用。在本研究中,对经氟化钠(NaF)处理的人骨肉瘤(HOS)细胞进行了短链非编码RNA(特别是miRNA和snoRNA)的整体表达谱分析,以了解它们在氟中毒发生发展中的可能作用。qPCR和电子杂交显示,miR-124和miR-155可能直接参与与Runt相关的转录因子2(RUNX2)和核因子κ-B配体受体激活剂(RANKL)基因的转录调控。与对照组相比,C/D盒分析显示,暴露于NaF的HOS细胞中UG二核苷酸和D盒序列的数量显著增加。在此,我们报告miR-124和miR-155是参与氟中毒发生发展的新的可能因素。我们表明,snoRNA的UG二核苷酸和D盒序列的改变可能是由于NaF暴露所致。