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biomill8358無(wú)蟲(chóng) (小有名氣)
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亨廷頓舞蹈癥發(fā)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 亨廷頓舞蹈癥發(fā)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. •亨廷頓舞蹈癥（HD）是一種無(wú)法治愈、神經(jīng)變性性疾病，目前仍缺乏有效的治療措施。正常的亨廷頓蛋白（HTT）和突變后的亨廷頓蛋白（mHTT）在體內(nèi)多組織表達(dá)，并能改變microRNAs（miRNAs）的轉(zhuǎn)錄。一些miRNAs可以以穩(wěn)定的形式存在于外周血中，近期已證實(shí)可作為幾種疾病標(biāo)志性檢測(cè)分子。 •本研究中，通過(guò)比較神經(jīng)元與非神經(jīng)元件miR表達(dá)差異，我們對(duì)HD標(biāo)志性miR進(jìn)行篩查。利用miR芯片方法，對(duì)過(guò)表達(dá)mHTT第一外顯子的細(xì)胞系進(jìn)行候選基因的篩查。之后，我們對(duì)候選miRNAs的血液穩(wěn)定性進(jìn)行了檢測(cè)。我們發(fā)現(xiàn)，miR-34b在mHTT第一外顯子的細(xì)胞系中表達(dá)量明顯升高，在體外，miR-34b能明顯減輕mHTT的毒性作用。通過(guò)檢測(cè)，miR-34存在于小血管血漿中，反復(fù)凍融后，降解不明顯。而且我們還發(fā)現(xiàn)，miR-34b在HD發(fā)病前的基因攜帶者血液中表達(dá)量上升。 ************************** [ Last edited by silicare on 2011-6-2 at 14:56 ] |
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