Experimental Therapeutics, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Gut. 2020 Apr;69(4):748-763. doi: 10.1136/gutjnl-2019-318279. Epub 2020 Feb 7.
One of the most unexpected discoveries in molecular oncology, in the last decades, was the identification of a new layer of protein coding gene regulation by transcripts that do not codify for proteins, the non-coding RNAs. These represent a heterogeneous category of transcripts that interact with many types of genetic elements, including regulatory DNAs, coding and other non-coding transcripts and directly to proteins. The final outcome, in the malignant context, is the regulation of any of the cancer hallmarks. Non-coding RNAs represent the most abundant type of hormones that contribute significantly to cell-to cell communication, revealing a complex interplay between tumour cells, tumour microenvironment cells and immune cells. Consequently, profiling their abundance in bodily fluids became a mainstream of biomarker identification. Therapeutic targeting of non-coding RNAs represents a new option for clinicians that is currently under development. This review will present the biology and translational value of three of the most studied categories on non-coding RNAs, the microRNAs, the long non-coding RNAs and the circular RNAs. We will also focus on some aspirational concepts that can help in the development of clinical applications related to non-coding RNAs, including using pyknons to discover new non-coding RNAs, targeting human-specific transcripts which are expressed specifically in the tumour cell and using non-coding RNAs to increase the efficiency of immunotherapy.
在过去几十年的分子肿瘤学中，最令人意想不到的发现之一是，鉴定出了一种新的转录本调控蛋白编码基因的方式，这些转录本不编码蛋白质，而是非编码 RNA。这些非编码 RNA 是一类具有异质性的转录本，它们与许多类型的遗传元件相互作用，包括调节 DNA、编码和其他非编码转录本，并直接与蛋白质相互作用。在恶性环境下，最终结果是调控任何癌症的标志性特征。非编码 RNA 是最丰富的激素类型之一，对细胞间通讯有重要贡献，揭示了肿瘤细胞、肿瘤微环境细胞和免疫细胞之间复杂的相互作用。因此，在体液中对其丰度进行分析已成为生物标志物鉴定的主流方法。非编码 RNA 的治疗靶向是临床医生正在开发的新选择。本文将介绍三种研究最广泛的非编码 RNA（microRNAs、长非编码 RNA 和环状 RNA）的生物学和转化价值。我们还将重点介绍一些有前途的概念，这些概念可以帮助开发与非编码 RNA 相关的临床应用，包括使用 pyknons 发现新的非编码 RNA、靶向仅在肿瘤细胞中特异性表达的人类特异性转录本，以及利用非编码 RNA 提高免疫疗法的效率。
