Deregulated microRNAs Involved in Prostate Cancer Aggressiveness and Treatment Resistance Mechanisms.
Deregulated microRNAs Involved in Prostate Cancer Aggressiveness and Treatment Resistance Mechanisms.
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越来越多的研究强调了 microRNA 在肿瘤发生和癌症治疗反应中的关键作用。在这里，我们系统地回顾了描述 microRNA 在前列腺癌发生和进展中的作用的科学出版物。大量研究表明，microRNA 靶向并调节与前列腺癌侵袭性和耐药性相关的关键基因。然而，microRNA 参与晚期和难治性前列腺癌的分子机制仍不清楚。本综述旨在强调当前与前列腺癌疾病中 microRNA 失调相关的理解和知识差距。此外，我们总结了基于 microRNA 的前列腺癌诊断/预后生物标志物和疗法的开发方面取得的有希望的进展。前列腺癌（PCa）是美国男性中最常诊断出的癌症，也是癌症死亡的第二大原因。 PCa 的发生和进展涉及复杂的遗传和表观遗传机制。 MicroRNA (miRNA) 是短非编码 RNA，通过靶向 mRNA 进行降解或抑制蛋白质翻译，在转录后水平调节蛋白质表达。在过去的二十年中，miRNA 研究领域迅速扩展，新的证据表明 miRNA 功能障碍是包括癌症在内的多种疾病的重要表观遗传机制。本文基于现有文献，重点了解失调的 miRNA 在 PCa 侵袭性和耐药性中的功能作用和分子机制。具体来说，讨论了 PCa 与正常组织、晚期 PCa 与低级别 PCa 以及治疗反应性与无反应性 PCa 中差异表达（上调或下调）的 miRNA。特别是，讨论和总结了参与以下调节的致癌和肿瘤抑制 miRNA：(1) 雄激素受体 (AR) 及其 AR-V7 剪接变体的合成，(2) PTEN 表达和 PTEN 介导的信号传导，(3) RNA 剪接机制，(4) 化疗和激素治疗耐药性，以及 (5) PCa 中的种族差异。我们进一步概述了基于 miRNA 的生物标志物和治疗方法在 PCa 诊断/预后和治疗临床实践中的当前进展和挑战。
Accumulating studies have highlighted the critical roles of microRNAs in tumorigenesis and cancer treatment responses. Here, we systematically review the scientific publications describing the roles of microRNAs in the development and progression of prostate cancer. Numerous studies have demonstrated that microRNAs target and regulate critical genes involved in prostate cancer aggressiveness and drug resistance. However, the molecular mechanisms underlying microRNA involvement in the advanced and treatment-resistant prostate cancers remain unclear. This review aims to highlight the current understanding and knowledge gap related to the deregulation of microRNAs in prostate cancer diseases. Furthermore, we summarize the promising progress on the development of microRNA-based diagnostic/prognostic biomarkers and therapies for prostate cancer. Prostate cancer (PCa) is the most frequently diagnosed cancer and the second leading cause of cancer deaths among American men. Complex genetic and epigenetic mechanisms are involved in the development and progression of PCa. MicroRNAs (miRNAs) are short noncoding RNAs that regulate protein expression at the post-transcriptional level by targeting mRNAs for degradation or inhibiting protein translation. In the past two decades, the field of miRNA research has rapidly expanded, and emerging evidence has revealed miRNA dysfunction to be an important epigenetic mechanism underlying a wide range of diseases, including cancers. This review article focuses on understanding the functional roles and molecular mechanisms of deregulated miRNAs in PCa aggressiveness and drug resistance based on the existing literature. Specifically, the miRNAs differentially expressed (upregulated or downregulated) in PCa vs. normal tissues, advanced vs. low-grade PCa, and treatment-responsive vs. non-responsive PCa are discussed. In particular, the oncogenic and tumor-suppressive miRNAs involved in the regulation of (1) the synthesis of the androgen receptor (AR) and its AR-V7 splice variant, (2) PTEN expression and PTEN-mediated signaling, (3) RNA splicing mechanisms, (4) chemo- and hormone-therapy resistance, and (5) racial disparities in PCa are discussed and summarized. We further provide an overview of the current advances and challenges of miRNA-based biomarkers and therapeutics in clinical practice for PCa diagnosis/prognosis and treatment.
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影响因子：
2.9
作者：
Liu SG;Qin XG;Zhao BS;Qi B;Yao WJ;Wang TY;Li HC;Wu XN
通讯作者：
Wu XN
影响因子：
2.7
作者：
Wang L;Gao J;Zhang Y;Kang S
通讯作者：
Kang S
DOI：
10.1016/j.biocel.2021.106096
发表时间：
2021-12
期刊：
The international journal of biochemistry & cell biology
影响因子：
--
作者：
Calderon-Aparicio A;Wang BD
通讯作者：
Wang BD
影响因子：
--
作者：
Zhang, Gongyi;Zhang, Rong;Bai, Ping;Li, Shumin;Zuo, Jing;Zhang, Yuanyuan;Liu, Mei;Wu, Lingying
通讯作者：
Wu, Lingying
影响因子：
--
作者：
Kim SJ;Ha JW;Zhang BT
通讯作者：
Zhang BT