已知一类自然存在的被称作microRNA(miRNA, miRNA, 即微RNA)的小片段核酸序列调节许多癌症的产生。如今，在一项新研究中，miRNA似乎在前列腺癌中发挥着至关重要的作用。直接靶向microRNA-125b(miRNA-125b)来阻断雄激素受体活性代表着一种治疗去势难治性前列腺癌的(castrate-resistant prostate cancer)新方法。这种大有希望的新策略可以改善抗雄激素和其他激素疗法的疗效。相关研究结果发表在BioResearch Open Access期刊上，题目为“miR-125b Regulation of Androgen Receptor Signaling Via Modulation of the Receptor Complex Co-Repressor NCOR2”。
在这项研究中，来自美国科罗拉多大学丹佛分校和明尼苏达大学的Xiaoping Yang、Lynne Bernis、Lih-Jen Su、Dexiang Gao和Thomas Flaig寻找有可能揭示miRNA-125b在调节前列腺癌中发挥作用的靶标，结果发现它直接抑制NCOR2，其中NCOR2发挥着抑制雄激素受体的作用。
论文作者们指出"雄激素受体是前列腺癌中一个至关重要的治疗靶标"，这种受体发生改变是产生去势难治性前列腺癌所必需的。在去势难治性前列腺癌中，激素疗法不能治疗这种疾病
苏格兰爱丁堡大学再生医学MRC中心教授、BioResearch Open Access期刊主编Jane Taylor博士说，“这项研究通过鉴定出miR-125b的一种新靶标而让人们对miR-125b调节去势难治性前列腺癌产生的机制产生新的认识。这项研究的临床意义在于靶向调节这种miRNA可能导致人们开发出更加有效的抗癌疗法。”(生物谷：Bioon.com)
本文编译自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.
