Mir-34: a new weapon against cancer?
Mir-34: a new weapon against cancer?
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DOI：
10.1038/mtna.2014.47
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发表时间：
2014-09-23
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microRNA(miRNA)-34a是肿瘤抑制的关键调节因子。它控制大量参与细胞周期、分化和凋亡的靶蛋白的表达，并拮抗基本癌细胞活力以及癌症干性、转移和化疗耐药所必需的过程。在这篇综述中，我们重点关注 miR-34a 介导的肿瘤抑制的分子机制，重点关注 miR-34a 的主要靶标以及参与该 miRNA 调节的主要调节因子。此外，我们还阐明了 miR-34a 在调节化疗反应中的作用以及植物营养素介导的癌细胞中 miR-34a 表达和活性的调节。鉴于 miR-34a 广泛的抗癌活性，我们还讨论了基于纳米技术递送 miRNA 模拟物的新治疗概念的实质性益处。事实上，抑癌基因 miRNA 的替代提供了一种对抗肿瘤异质性的有效策略，而基于 RNA 的选择性递送系统似乎是安全有效靶向肿瘤的绝佳平台。
The microRNA(miRNA)-34a is a key regulator of tumor suppression. It controls the expression of a plethora of target proteins involved in cell cycle, differentiation and apoptosis, and antagonizes processes that are necessary for basic cancer cell viability as well as cancer stemness, metastasis, and chemoresistance. In this review, we focus on the molecular mechanisms of miR-34a-mediated tumor suppression, giving emphasis on the main miR-34a targets, as well as on the principal regulators involved in the modulation of this miRNA. Moreover, we shed light on the miR-34a role in modulating responsiveness to chemotherapy and on the phytonutrients-mediated regulation of miR-34a expression and activity in cancer cells. Given the broad anti-oncogenic activity of miR-34a, we also discuss the substantial benefits of a new therapeutic concept based on nanotechnology delivery of miRNA mimics. In fact, the replacement of oncosuppressor miRNAs provides an effective strategy against tumor heterogeneity and the selective RNA-based delivery systems seems to be an excellent platform for a safe and effective targeting of the tumor.
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