In order to identify new targets and treatment modalities for clear cell renal carcinoma, we surveyed the literature with respect to microRNAs involved in this disease. In this review, we have focused on up- and down-regulated miRs which mediate efficacy in preclinical clear-cell renal carcinoma-related in vivo models. We have identified 10 up-regulated and 33 down-regulated micro-RNAs according to this criterion. As proof-of-concept, micro-RNAs interfering with VEGF (miR-205p) and mTOR (mir-99a) pathways, which are modulated by approved drugs for this disease, have been identified. miRs targeting hypoxia induced factor-2α (HIF-2α) (miR-145), E3 ubiquitinylases speckle-type POZ protein (SPOP) (miR 520/372/373) and casitas B-lineage lymphoma (CBL) (miR-200a-3p), interfere with druggable targets. Further identified miRs interfere with cell-cycle dependent kinases, such as CDK2 (miR-200c), CDK4, 6 (miR-1) and CDK4, 9 (206c). Transmembrane receptor Ral interacting protein of 76 kD (RLIP76), targeted by mir-137, has emerged as another important target for ccRCC. Additional miRs and their targets merrying further preclinical validation are discussed.

中文翻译：

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透明细胞肾癌：MicroRNA 在临床前体内模型中具有功效。


为了确定透明细胞肾癌的新靶点和治疗方式，我们调查了有关该疾病涉及的 microRNA 的文献。在这篇综述中，我们重点关注上调和下调的 miR，这些 miR 介导临床前透明细胞肾癌相关体内模型的功效。根据此标准，我们鉴定了 10 个上调的 micro-RNA 和 33 个下调的 micro-RNA。作为概念验证，已经确定了干扰 VEGF (miR-205p) 和 mTOR (mir-99a) 通路的 micro-RNA，这些通路由批准用于治疗这种疾病的药物调节。靶向缺氧诱导因子 2α (HIF-2α) (miR-145)、E3 泛素化酶斑点型 POZ 蛋白 (SPOP) (miR 520/372/373) 和 casitas B 系淋巴瘤 (CBL) (miR-200a-) 的 miR 3p)，干扰可药物靶点。进一步鉴定的 miR 会干扰细胞周期依赖性激酶，例如 CDK2 (miR-200c)、CDK4, 6 (miR-1) 和 CDK4, 9 (206c)。 mir-137 靶向的 76 kD 跨膜受体 Ral 相互作用蛋白 (RLIP76) 已成为 ccRCC 的另一个重要靶点。讨论了其他 miR 及其需要进一步临床前验证的靶点。