已知一類自然存在的被稱作microRNA(miRNA, miRNA, 即微RNA)的小片段核酸序列調(diào)節(jié)許多癌癥的產(chǎn)生。如今,，在一項新研究中,，miRNA似乎在前列腺癌中發(fā)揮著至關(guān)重要的作用。直接靶向microRNA-125b(miRNA-125b)來阻斷雄激素受體活性代表著一種治療去勢難治性前列腺癌的(castrate-resistant prostate cancer)新方法,。這種大有希望的新策略可以改善抗雄激素和其他激素療法的療效,。相關(guān)研究結(jié)果發(fā)表在BioResearch Open Access期刊上，題目為“miR-125b Regulation of Androgen Receptor Signaling Via Modulation of the Receptor Complex Co-Repressor NCOR2”,。
在這項研究中,，來自美國科羅拉多大學(xué)丹佛分校和明尼蘇達大學(xué)的Xiaoping Yang、Lynne Bernis,、Lih-Jen Su,、Dexiang Gao和Thomas Flaig尋找有可能揭示miRNA-125b在調(diào)節(jié)前列腺癌中發(fā)揮作用的靶標(biāo)，結(jié)果發(fā)現(xiàn)它直接抑制NCOR2,，其中NCOR2發(fā)揮著抑制雄激素受體的作用,。
論文作者們指出"雄激素受體是前列腺癌中一個至關(guān)重要的治療靶標(biāo)"，這種受體發(fā)生改變是產(chǎn)生去勢難治性前列腺癌所必需的,。在去勢難治性前列腺癌中,，激素療法不能治療這種疾病
蘇格蘭愛丁堡大學(xué)再生醫(yī)學(xué)MRC中心教授、BioResearch Open Access期刊主編Jane Taylor博士說,，“這項研究通過鑒定出miR-125b的一種新靶標(biāo)而讓人們對miR-125b調(diào)節(jié)去勢難治性前列腺癌產(chǎn)生的機制產(chǎn)生新的認(rèn)識,。這項研究的臨床意義在于靶向調(diào)節(jié)這種miRNA可能導(dǎo)致人們開發(fā)出更加有效的抗癌療法。”(生物谷：Bioon.com)
本文編譯自http://medicalxpress.com/news/2012-07-therapeutic-prostate-cancer.html
doi:10.1089/biores.2012.9903
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miR-125b Regulation of Androgen Receptor Signaling Via Modulation of the Receptor Complex Co-Repressor NCOR2
Xiaoping Yang, Lynne Bemis, Lih-Jen Su, Dexiang Gao, and Thomas W. Flaig
Recognition of micro-RNA function and their contribution to the biology of disease has given a new insight into disease mechanisms, with these discoveries potentially improving clinical diagnostic and therapeutic options. miR-125b has been identified as an important regulator in various cancers, including prostate cancer, but the mechanism of this regulation remains incompletely understood. In these studies, the effect of castration on miR-125b serum expression was evaluated in mice, simulating androgen deprivation. Furthermore, miR-125b expression was measured by quantitative real-time polymerase chain reaction (qRT-PCR) in LNCaP prostate cancer cells treated with the antiandrogen bicalutamide. Using LNCaP cells, the effect of miR-125b modulation on apoptotic protein and NCOR2, a co-repressor of androgen receptor (AR), was examined by Western blot. A 3′-untranslated region (UTR) luciferase-binding assay was performed to confirm that miR-125b targets NCOR2. We found that surgical castration induced an initial increase in the expression of circulating miR-125b in mice, while sham surgery did not. In addition, AR blockade via bicalutamide was associated with the rapid release of miR-125b into the cell culture medium of prostate cancer cells. A previously studied target of miR-125b, a regulator in the apoptotic pathway, BAK1, could not completely account for the role of miR-125b in prostate cancer. Thus, we looked for additional targets of miR-125b and found that NCOR2, which is a repressor of AR, is a direct target of miR-125b. We found that NCOR2 protein expression was blocked by mimics of miR-125b, and a luciferase-binding assay confirmed that NCOR2 is a direct target of miR-125b. Our data provide novel evidence that miR-125b is an important regulator of the AR with specific ramification for the effectiveness of antiandrogens and other hormonal therapies in prostate cancer.
