Long non-coding RNAs are important regulators of gene expression and diverse biological processes. Their aberrant expression contributes to a verity of diseases including cancer development and progression, providing them with great potential to be diagnostic and prognostic biomarkers and therapeutic targets. Therefore, they can have a key role in personalized cancer medicine. This review aims at introducing possible strategies to target long ncRNAs therapeutically in cancer. Also, chemical modification of nucleic acid-based therapeutics to improve their pharmacological properties is explained. Then, approaches for the systematic delivery of reagents into the tumor cells or organs are briefly discussed, followed by describing obstacles to the expansion of the therapeutics. Long ncRNAs function as oncogenes or tumor suppressors, whose activity can modulate all hallmarks of cancer. They are expressed in a very restricted spatial and temporal pattern and can be easily detected in the cells or biological fluids of patients. These properties make them excellent targets for the development of anticancer drugs. Targeting methods aim to attenuate oncogenic lncRNAs or interfere with lncRNA functions to prevent carcinogenesis. Numerous strategies including suppression of oncogenic long ncRNAs, alternation of their epigenetic effects, interfering with their function, restoration of downregulated or lost long ncRNAs, and recruitment of long ncRNAs regulatory elements and expression patterns are recommended for targeting long ncRNAs therapeutically in cancer. These approaches have shown inhibitory effects on malignancy. In this regard, proliferation, migration, and invasion of tumor cells have been inhibited and apoptosis has been induced in different cancer cells in vitro and in vivo. Downregulation of oncogenic long ncRNAs and upregulation of some growth factors (e.g., neurotrophic factor) have been achieved. Targeting long non-coding RNAs therapeutically in cancer and efficient and safe delivery of the reagents have been rarely addressed. Only one clinical trial involving lncRNAs has been reported. Among different technologies, RNAi is the most commonly used and effective tool to target lncRNAs. However, other technologies need to be examined and further research is essential to put lncRNAs into clinical practice.

中文翻译：

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在癌症治疗中靶向长链非编码 RNA 的策略：进展与挑战

长链非编码 RNA 是基因表达和多种生物过程的重要调节因子。它们的异常表达有助于多种疾病，包括癌症的发展和进展，为它们提供了成为诊断和预后生物标志物和治疗靶点的巨大潜力。因此，它们可以在个性化癌症医学中发挥关键作用。本综述旨在介绍在癌症中治疗靶向长 ncRNA 的可能策略。此外，还解释了基于核酸的治疗剂的化学修饰以改善其药理特性。然后，简要讨论了将试剂系统递送到肿瘤细胞或器官中的方法，然后描述了治疗扩展的障碍。长 ncRNA 具有致癌基因或肿瘤抑制基因的功能，其活动可以调节癌症的所有特征。它们以非常有限的空间和时间模式表达，可以很容易地在患者的细胞或生物体液中检测到。这些特性使它们成为开发抗癌药物的绝佳靶点。靶向方法旨在减弱致癌 lncRNA 或干扰 lncRNA 功能以防止致癌。许多策略，包括抑制致癌长 ncRNA、改变其表观遗传效应、干扰其功能、恢复下调或丢失的长 ncRNA，以及招募长 ncRNA 调控元件和表达模式，都被推荐用于治疗癌症中的长 ncRNA。这些方法已显示出对恶性肿瘤的抑制作用。在这方面，扩散、迁移、在体外和体内不同的癌细胞中，肿瘤细胞的侵袭受到抑制并诱导细胞凋亡。已经实现了致癌长 ncRNA 的下调和一些生长因子（例如神经营养因子）的上调。在癌症中治疗性靶向长链非编码 RNA 以及有效和安全地递送试剂很少被解决。仅报道了一项涉及 lncRNA 的临床试验。在不同的技术中，RNAi 是最常用和最有效的靶向 lncRNA 的工具。然而，还需要检查其他技术，进一步的研究对于将 lncRNA 应用于临床实践至关重要。神经营养因子）。在癌症中治疗性靶向长链非编码 RNA 以及有效和安全地递送试剂很少被解决。仅报道了一项涉及 lncRNA 的临床试验。在不同的技术中，RNAi 是最常用和最有效的靶向 lncRNA 的工具。然而，还需要检查其他技术，进一步的研究对于将 lncRNA 应用于临床实践至关重要。神经营养因子）。在癌症中治疗性靶向长链非编码 RNA 以及有效和安全地递送试剂很少被解决。仅报道了一项涉及 lncRNA 的临床试验。在不同的技术中，RNAi 是最常用和最有效的靶向 lncRNA 的工具。然而，还需要检查其他技术，进一步的研究对于将 lncRNA 应用于临床实践至关重要。