Department of Pharmacology, Case Western Reserve University, Cleveland, OH, 44106, USA.
Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH, 44106, USA.
Semin Cancer Biol. 2022 Jan;78:23-34. doi: 10.1016/j.semcancer.2021.03.020. Epub 2021 Mar 26.
Tumor dormancy is a major contributor to the lethality of metastatic disease, especially for cancer patients who develop metastases years-to-decades after initial diagnosis. Indeed, tumor cells can disseminate during early disease stages and persist in new microenvironments at distal sites for months, years, or even decades before initiating metastatic outgrowth. This delay between primary tumor remission and metastatic relapse is known as "dormancy," during which disseminated tumor cells (DTCs) acquire quiescent states in response to intrinsic (i.e., cellular) and extrinsic (i.e., microenvironmental) signals. Maintaining dormancy-associated phenotypes requires DTCs to activate transcriptional, translational, and post-translational mechanisms that engender cellular plasticity. RNA processing is emerging as an essential facet of cellular plasticity, particularly with respect to the initiation, maintenance, and reversal of dormancy-associated phenotypes. Moreover, dysregulated RNA processing, particularly that associated with alternative RNA splicing and expression of noncoding RNAs (ncRNAs), can occur in DTCs to mediate intrinsic and extrinsic metastatic dormancy. Here we review the pathophysiological impact of alternative RNA splicing and ncRNAs in promoting metastatic dormancy and disease recurrence in human cancers.
肿瘤休眠是转移疾病致命性的主要原因，特别是对于那些在初始诊断后数年至数十年才发展为转移的癌症患者。事实上，肿瘤细胞可以在早期疾病阶段扩散，并在新的微环境中持续存在数月、数年甚至数十年，然后才开始转移生长。这种原发性肿瘤缓解和转移性复发之间的延迟被称为“休眠”，在此期间，播散的肿瘤细胞（DTCs）会根据内在（即细胞）和外在（即微环境）信号，进入静止状态。维持休眠相关表型需要 DTCs 激活转录、翻译和翻译后机制，从而产生细胞可塑性。RNA 处理作为细胞可塑性的一个重要方面正在出现，特别是在休眠相关表型的起始、维持和逆转方面。此外，DTC 中可能会发生失调的 RNA 处理，特别是与选择性 RNA 剪接和非编码 RNA（ncRNA）表达相关的 RNA 处理，以介导内在和外在的转移性休眠。在这里，我们综述了选择性 RNA 剪接和 ncRNA 在促进人类癌症中的转移休眠和疾病复发中的病理生理影响。
