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亨廷顿舞蹈症发病前血液中Hsa-miR-34b 含量上升
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Hsa-miR-34b is a plasma-stable microRNA that is elevated in pre-manifest Huntington’s disease 亨廷顿舞蹈症发病前血液中Hsa-miR-34b 含量上升 Maria Bjo ¨rkqvist 2011 Human Molecular Genetics 摘要：Huntington’s disease (HD) is a devastating, neurodegenerative condition, which lacks effective treatment.Normal Huntingtin (HTT) and mutant Huntingtin (mHTT) are expressed in multiple tissues and can alter transcription of microRNAs (miRs). Importantly, miRs are present in a bio-stable form in human peripheral bloodplasma and have recently been shown to be useful biomarkers in other diseases. We therefore sought toidentify potential miR biomarkers of HD that are present in, and have functional consequences for, neuronaland non-neuronal tissues. In a cell line over-expressing mHTT-Exon-1, miR microarray analysis was used toidentify candidate miRs. We then examined their presence and bio-stability in control and HD plasma. Wefound that miR-34b is significantly elevated in response to mHTT-Exon-1, and its blockade alters the toxicityof mHTT-Exon-1 in vitro. We also show that miR-34b is detectable in plasma from small input volumes and isinsensitive to freeze-thaw-induced RNA degradation. Interestingly, miR-34b is significantly elevated inplasma from HD gene carriers prior to symptom onset. This is the first study suggesting that plasma miRs might be used as biomarkers for HD. •亨廷顿舞蹈症（HD）是一种无法治愈、神经变性性疾病，目前仍缺乏有效的治疗措施。正常的亨廷顿蛋白（HTT）和突变后的亨廷顿蛋白（mHTT）在体内多组织表达，并能改变microRNAs（miRNAs）的转录。一些miRNAs可以以稳定的形式存在于外周血中，近期已证实可作为几种疾病标志性检测分子。 •本研究中，通过比较神经元与非神经元件miR表达差异，我们对HD标志性miR进行筛查。利用miR芯片方法，对过表达mHTT第一外显子的细胞系进行候选基因的筛查。之后，我们对候选miRNAs的血液稳定性进行了检测。我们发现，miR-34b在mHTT第一外显子的细胞系中表达量明显升高，在体外，miR-34b能明显减轻mHTT的毒性作用。通过检测，miR-34存在于小血管血浆中，反复冻融后，降解不明显。而且我们还发现，miR-34b在HD发病前的基因携带者血液中表达量上升。 ************************** [ Last edited by silicare on 2011-6-2 at 14:56 ] |
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