Ebrahimi Safieh, Hashemy Seyed Isaac, Sahebkar Amirhossein, Aghaee Bakhtiari Seyed Hamid
Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
Curr Mol Pharmacol. 2021 Oct 25;14(4):559-569. doi: 10.2174/1874467213666201223121850.
Prostate cancer (PCa) is the second most prevalent cancer and the fifth leading cause of cancer-related deaths among men. Androgen deprivation therapy (ADT) is the most frequently used therapeutic strategy in PCa; however, the development of resistance to ADT, known as castration- resistant prostate cancer (CRPC), continues to be a major obstacle against the successful treatment of PCa. The abnormal activation of the androgen receptor (AR) signaling pathway has been found as one of the main contributing factors to the development of resistance in CRPC. Therefore, AR regulatory strategies are urgently required to combat resistance. Recently, microRNAs (miRNAs) have been found as major AR regulatory factors affecting ADT resistance. MiRNAs can target AR itself, AR-related genes, AR splice variants, AR-related signaling pathways as well as cancer stem cells (CSCs), and play critical roles in regulating ADT resistance. Due to their capability to affect various genes and signaling pathways, miRNAs are now being studied for their potential role as a new therapeutic target in CRPC. It has been recommended that combination therapies, including miRNAs and existing drugs, can synergistically decrease castration resistance. miRNAs also have prognostic values for ADT, and their expression profiling in CRPC patients before therapeutic scheduling may enable the physician to diagnose patients who are ADT-resistant. Overall, extant evidence obviously supports the predictive and therapeutic potential of miRNAs in CRPC patients. This review summarizes the available information about the microRNA-mediated AR controlling mechanisms involved in ADT resistance.
前列腺癌（PCa）是男性中第二常见的癌症，也是癌症相关死亡的第五大主要原因。雄激素剥夺疗法（ADT）是PCa中最常用的治疗策略；然而，对ADT产生耐药性，即去势抵抗性前列腺癌（CRPC）的发展，仍然是成功治疗PCa的主要障碍。雄激素受体（AR）信号通路的异常激活已被发现是CRPC耐药性发展的主要促成因素之一。因此，迫切需要AR调控策略来对抗耐药性。最近，微小RNA（miRNA）已被发现是影响ADT耐药性的主要AR调控因子。miRNA可以靶向AR本身、AR相关基因、AR剪接变体、AR相关信号通路以及癌症干细胞（CSC），并在调节ADT耐药性中发挥关键作用。由于其能够影响各种基因和信号通路，目前正在研究miRNA作为CRPC新治疗靶点的潜在作用。有人建议，包括miRNA和现有药物在内的联合疗法可以协同降低去势抵抗性。miRNA对ADT也具有预后价值，在治疗安排前对CRPC患者进行miRNA表达谱分析可能使医生能够诊断出对ADT耐药的患者。总体而言，现有证据明显支持miRNA在CRPC患者中的预测和治疗潜力。本综述总结了有关miRNA介导的AR调控机制参与ADT耐药性的现有信息。
