MiR-455-3p inhibits the degenerate process of chondrogenic differentiation through modification of DNA methylation.
MiR-455-3p inhibits the degenerate process of chondrogenic differentiation through modification of DNA methylation.
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MiR-455-3p 通过修饰 DNA 甲基化抑制软骨分化的简并过程
DOI：
10.1038/s41419-018-0565-2
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发表时间：
2018-05-01
影响因子：
9
通讯作者：
Zhang Z
中科院分区：
文献类型：
--
作者：
Sun H;Zhao X;Zhang C;Zhang Z;Lun J;Liao W;Zhang Z
这项工作的目的是确定miR-455-3p是否调节hMSCs软骨分化过程中的DNA甲基化。miR-455-3p和新生甲基转移酶DNMT3A的表达在体外诱导成软骨分化的hBMSCs和体内E16.5小鼠的微质量培养中进行了评估。荧光素酶报告基因检测证实miR-455-3p是否通过与3 ' -UTR相互作用直接靶向DNMT3A。使用Illumina Infinium甲基化EPIC微阵列，在诱导的软骨分化过程中检测具有或不具有过表达miR-455-3p的hBMSCs的全基因组DNA甲基化28天。在这里，我们发现miR-455-3p在hBMSC软骨分化的中期表达较多，而在晚期表达较少。DNMT3A在miR-455-3p缺失小鼠的中期表达量较少，晚期表达量较多，并且与野生型小鼠相比，DNMT3A在miR-455-3p缺失小鼠的手掌中表达量也较多。荧光素酶报告基因实验表明，miR-455-3p直接靶向DNMT3A 3 ' -UTR。miR-455-3p过表达抑制软骨分化过程中的退变过程，而小鼠中miR-455-3p缺失加速软骨退变。全基因组DNA甲基化分析显示，miR-455-3p过表达调节软骨特异性基因的DNA甲基化。氧化石墨烯分析显示，PI3K-Akt信号通路的低甲基化程度最高。我们的数据表明，miR-455-3p可以通过影响DNA甲基化来调节hMSC软骨分化。因此，miR-455-3p和DNA甲基化抑制剂的过表达可以潜在地用于优化软骨分化。
The aim of this work was to determine whether miR-455-3p regulates DNA methylation during chondrogenic differentiation of hMSCs. The expression of miR-455-3p and de novo methyltransferase DNMT3A was assessed in micromass culture of hBMSCs, which induced chondrogenic differentiation in vitro, and in E16.5 mice in vivo. A luciferase reporter assay was used to confirm whether miR-455-3p directly targets DNMT3A by interaction with the 3′-UTR. Using an Illumina Infinium Methylation EPIC microarray, genome-wide DNA methylation of hBMSCs with or without overexpressed miR-455-3p was examined for 28 days during induced chondrogenic differentiation. Here, we showed that miR-455-3p was more expressed during the middle stage of hBMSC chondrogenic differentiation, and less expressed in the late stage. DNMT3A was less expressed in the middle stage and more expressed in the late stage, and was also more expressed in the palms of miR-455-3p deletion mice compared to those of wild-type mice. The luciferase reporter assay demonstrated that miR-455-3p directly targets DNMT3A 3′-UTR. miR-455-3p overexpression inhibits the degenerate process during chondrogenic differentiation, while deletion of miR-455-3p in mice accelerated cartilage degeneration. Genome-wide DNA methylation analysis showed miR-455-3p overexpression regulates DNA methylation of cartilage-specific genes. GO analysis revealed PI3K-Akt signaling pathway was most hypomethylated. Our data show that miR-455-3p can regulate hMSC chondrogenic differentiation by affecting DNA methylation. Overexpression of miR-455-3p and DNA methylation inhibitors can thus potentially be utilized to optimize chondrogenic differentiation.
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DOI：
10.1590/1414-431x20165988
发表时间：
2017-02-16
期刊：
Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas
影响因子：
--
作者：
Wang H;Shan XB;Qiao YJ
通讯作者：
Qiao YJ
影响因子：
12.4
作者：
Pellacani, D.;Kestoras, D.;Maitland, N. J.
通讯作者：
Maitland, N. J.
影响因子：
9
作者：
Lalevée S;Lapaire O;Bühler M
通讯作者：
Bühler M
MicroRNA-381 通过抑制组蛋白脱乙酰酶 4 表达来调节软骨细胞肥大
影响因子：
5.6
作者：
Chen W;Sheng P;Huang Z;Meng F;Kang Y;Huang G;Zhang Z;Liao W;Zhang Z
通讯作者：
Zhang Z
影响因子：
14.9
作者：
Gatto S;Gagliardi M;Franzese M;Leppert S;Papa M;Cammisa M;Grillo G;Velasco G;Francastel C;Toubiana S;D'Esposito M;Angelini C;Matarazzo MR
通讯作者：
Matarazzo MR