近日,，英國倫敦帝國理工學(xué)院研究人員發(fā)現(xiàn)一個名為miR-27a的分子,，其在促使前列腺癌癥腫瘤生長過程中扮演著重要角色，未來可能成為前列腺癌癥治療的一個新靶點,。這一研究成果發(fā)表在《人類分子遺傳學(xué)》(Human Molecular Genetics)雜志上,。
前列腺癌是發(fā)生于男性前列腺組織中的惡性腫瘤。在歐美，它是男性最?；嫉陌┌Y之一,，僅在英國，每年就有大約36000人被診斷出患上該種疾病,。前列腺癌的確切病因至今尚未明確,，據(jù)信如基因和飲食等多種因素與其有關(guān)。而前列腺癌癥腫瘤的生長則與雄性激素有關(guān),，雄性激素會刺激癌細(xì)胞分裂,，進(jìn)而促使腫瘤生長。
倫敦帝國理工學(xué)院研究人員在實驗中發(fā)現(xiàn),，雄性激素會增加前列腺癌細(xì)胞中一種名為miR-27a的分子的數(shù)量,，而這種分子對癌細(xì)胞生長具有極大的刺激作用，抑制這種分子,，會使得前列腺癌細(xì)胞的生長速率降低一半,。這表明，miR-27a這種分子極有可能成為前列腺癌癥治療的一個新靶點,。
miR-27a屬于微核糖核酸（microRNA）,。微核糖核酸在調(diào)節(jié)基因活動方面具有重要作用，相比于蛋白質(zhì),，微核糖核酸更易設(shè)計,，也更易合成可輕易進(jìn)入細(xì)胞內(nèi)部的抑制分子，因而作為一個新的治療靶點,，科學(xué)家們對其更加看好,。
論文第一作者、帝國理工學(xué)院的克萊爾·弗萊徹表示,，新研究表明,，miR-27a是雄性激素與前列腺腫瘤兩者間的一個重要媒介，有可能成為前列腺治療新方法的靶點,。目前已經(jīng)證明,，在實驗室中，抑制miR-27a分子就可以抑制前列腺腫瘤的生長,，但這只是研究的第一步,，未來還有許多障礙需要克服。他們下一步研究目標(biāo)是要通過動物實驗來對研究成果進(jìn)行進(jìn)一步驗證,，而要開發(fā)出適用于人類的新療法,，則至少還需要幾年的時間。（生物谷Bioon.com）
doi: 10.1093/hmg/dds139
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Androgen-regulated processing of the oncomir MiR-27a, which targets Prohibitin in prostate cancer
Claire E. Fletcher1, D. Alwyn Dart1, Ailsa Sita-Lumsden1, Helen Cheng2, Paul S. Rennie2 and Charlotte L. Bevan1,*
MicroRNAs (miRs) play an important role in the development of many complex human diseases and may have tumour suppressor or oncogenic (oncomir) properties. Prostate cancer is initially an androgen-driven disease, and androgen receptor (AR) remains a key driver of growth even in castration-resistant tumours. However, AR-mediated oncomiR pathways remain to be elucidated. We demonstrate that miR-27a is an androgen-regulated oncomir in prostate cancer, acting via targeting the tumour suppressor and AR corepressor, Prohibitin (PHB). Increasing miR-27a expression results in reduced PHB mRNA and protein levels, and increased expression of AR target genes and prostate cancer cell growth. This involves a novel mechanism for androgen-mediated miR regulation, whereby AR induces a transient increase in miR-23a27a24-2 transcription, but more significantly accelerates processing of the primiR-23a27a24-2 cluster. Androgens therefore regulate miR-27a expression both transcriptionally (via AR binding to the cluster promoter) and post-transcriptionally (accelerating primiR processing to the mature form). We further show that a miR-27a anti-sense oligonucleotide, by opposing the effects of mir-27a, has therapeutic potential in prostate cancer.
