Gugnoni Mila, Kashyap Manoj Kumar, Wary Kishore K, Ciarrocchi Alessia
Laboratory of Translational Research, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, Italy.
Molecular Oncology Laboratory, Amity Stem Cell Institute, Amity Medical School, Amity University Haryana, Panchgaon (Manesar), Gurugram, Haryana, India.
Mol Cancer. 2025 Jan 31;24(1):38. doi: 10.1186/s12943-025-02236-7.
Cancer progression relies on the ability of cells to adapt to challenging environments overcoming stresses and growth constraints. Such adaptation is a multifactorial process that depends on the rapid reorganization of many basic cellular mechanisms. Protein synthesis is often dysregulated in cancer, and translational reprogramming is emerging as a driving force of cancer adaptive plasticity. Long non-coding RNAs (lncRNAs) represent the main product of genome transcription. They outnumber mRNAs by an order of magnitude and their expression is regulated in an extremely specific manner depending on context, space and time. This heterogeneity is functional and allows lncRNAs to act as context-specific, fine-tuning controllers of gene expression. Multiple recent evidence underlines how, besides their consolidated role in transcription, lncRNAs are major players in translation control. Their capacity to establish multiple and highly dynamic interactions with proteins and other transcripts makes these molecules able to play a central role across all phases of protein synthesis. Even if through a myriad of different mechanisms, the action of these transcripts is dual. On one hand, by modulating the overall translation speed, lncRNAs participate in the process of metabolic adaptation of cancer cells under stress conditions. On the other hand, by prioritizing the synthesis of specific transcripts they help cancer cells to maintain high levels of essential oncogenes. In this review, we aim to discuss the most relevant evidence regarding the involvement of lncRNAs in translation regulation and to discuss how this specific function may affect cancer plasticity and resistance to stress. We also expect to provide one of the first collective perspectives on the way these transcripts modulate gene expression beyond transcription.
癌症进展依赖于细胞适应具有挑战性的环境、克服压力和生长限制的能力。这种适应是一个多因素过程，取决于许多基本细胞机制的快速重组。蛋白质合成在癌症中常常失调，而翻译重编程正成为癌症适应性可塑性的驱动力。长链非编码RNA（lncRNA）是基因组转录的主要产物。它们的数量比mRNA多出一个数量级，并且其表达根据背景、空间和时间以极其特定的方式受到调控。这种异质性具有功能，使lncRNA能够作为基因表达的背景特异性微调控制器。最近的多项证据强调，除了在转录中已确立的作用外，lncRNA还是翻译控制的主要参与者。它们与蛋白质和其他转录本建立多种高度动态相互作用的能力，使这些分子能够在蛋白质合成的所有阶段发挥核心作用。即使通过无数不同的机制，这些转录本的作用也是双重的。一方面，通过调节整体翻译速度，lncRNA参与应激条件下癌细胞的代谢适应过程。另一方面，通过优先合成特定转录本，它们帮助癌细胞维持高水平的必需癌基因。在这篇综述中，我们旨在讨论关于lncRNA参与翻译调控的最相关证据，并讨论这种特定功能如何影响癌症可塑性和对压力的抗性。我们还期望提供关于这些转录本如何在转录之外调节基因表达的首批综合性观点之一。
