Institute of Biochemistry, Emil-Fischer-Zentrum, Friedrich-Alexander-University Erlangen-Nürnberg, 91054 Erlangen, Germany.
Comprehensive Cancer Center (CCC) Erlangen-EMN, 91054 Erlangen, Germany.
Cells. 2020 Jan 2;9(1):114. doi: 10.3390/cells9010114.
In this review, we summarize the current knowledge on miRNAs as therapeutic targets in two cancer types that were frequently described to be driven by miRNAs-melanoma and hepatocellular carcinoma (HCC). By focusing on common microRNAs and associated pathways in these-at first sight-dissimilar cancer types, we aim at revealing similar molecular mechanisms that are evolved in microRNA-biology to drive cancer progression. Thereby, we also want to outlay potential novel therapeutic strategies. After providing a brief introduction to general miRNA biology and basic information about HCC and melanoma, this review depicts prominent examples of potent oncomiRs and tumor-suppressor miRNAs, which have been proven to drive diverse cancer types including melanoma and HCC. To develop and apply miRNA-based therapeutics for cancer treatment in the future, it is essential to understand how miRNA dysregulation evolves during malignant transformation. Therefore, we highlight important aspects such as genetic alterations, miRNA editing and transcriptional regulation based on concrete examples. Furthermore, we expand our illustration by focusing on miRNA-associated proteins as well as other regulators of miRNAs which could also provide therapeutic targets. Finally, design and delivery strategies of miRNA-associated therapeutic agents as well as potential drawbacks are discussed to address the question of how miRNAs might contribute to cancer therapy in the future.
在这篇综述中，我们总结了当前关于 miRNA 作为两种癌症类型治疗靶点的知识，这两种癌症类型经常被描述为受 miRNA 驱动——黑色素瘤和肝细胞癌 (HCC)。通过关注这些在表面上不同的癌症类型中常见的微小 RNA 及其相关途径，我们旨在揭示驱动癌症进展的 miRNA 生物学中的相似分子机制。因此，我们还想提出潜在的新的治疗策略。在简要介绍一般 miRNA 生物学以及 HCC 和黑色素瘤的基本信息后，本综述描述了已被证明可驱动多种癌症类型（包括黑色素瘤和 HCC）的显著的致癌 miRNA 和肿瘤抑制 miRNA 例子。为了在未来开发和应用 miRNA 为基础的癌症治疗方法，了解 miRNA 失调在恶性转化过程中是如何演变的至关重要。因此，我们根据具体实例强调了遗传改变、miRNA 编辑和转录调控等重要方面。此外，我们通过关注 miRNA 相关蛋白以及其他 miRNA 调节剂，进一步扩展我们的说明，它们也可以作为治疗靶点。最后，讨论了 miRNA 相关治疗剂的设计和递送策略以及潜在的缺点，以解决 miRNA 如何有助于未来癌症治疗的问题。
