J Dent Res:MiR-335-3p在遗传性牙龈纤维瘤中的抗纤维化潜力

2019-07-22 lishiting MedSci原创

遗传性牙龈纤维瘤(HGF)是一种遗传性较高的异质性疾病,目前主要的治疗手段为手术切除但复发率较高。MicroRNAs (miRNAs)具有调整大规模靶向基因的能力。这篇研究的目的是基于目前可得到的miRNA靶向预测算法建立一种简单但有效的计算机策略以精确定位大多数能够负向调节基因功能的有效miRNA。

遗传性牙龈纤维瘤(HGF)是一种遗传性较高的异质性疾病,目前主要的治疗手段为手术切除但复发率较高。MicroRNAs (miRNAs)具有调整大规模靶向基因的能力。这篇研究的目的是基于目前可得到的miRNA靶向预测算法建立一种简单但有效的计算机策略以精确定位大多数能够负向调节基因功能的有效miRNA。

基于此种策略,miR-335-3p被层层筛选出来,它能够靶向HGF患者85种已知的促纤维化基因和79种表达上调的基因。实验室研究发现,与正常对照相比,HGF来源的牙龈成纤维细胞和TGF-b刺激的正常人牙龈成纤维细胞(NHGFs)中miR-335-3p表达下调。miR-335-3p通过经典和非经典的基础配对直接机械靶向SOS1, SMAD2/3和CTNNB1。特别是,当分别沉默SOS1, SMAD2/3或CTNNB1时,会抑制不同文献报道的纤维化标志物。

这篇研究第一次提出通过一种全新的miRNA筛查方法靶向定位功能性相关基因组,并鉴定出miR-335-3p为HGF治疗的一个全新靶点。miR-335-3p通过在促纤维化网络中机械复压多个核分子抑制人牙龈成纤维细胞的纤维化活性。这种治疗策略为HGF以及其他疾病的治疗提供了一种全新的模板。

原始出处:

Gao Q, Yang K, et al. Antifibrotic Potential of MiR-335-3p in Hereditary Gingival Fibromatosis. J Dent Res. 2019 Jul 19:22034519863300. doi: 10.1177/0022034519863300.

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    2019-12-21 smallant2002
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