Yan Yueren, Ren Yunpeng, Bao Yufang, Wang Yongbo
Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
Department of Cellular and Genetic Medicine, Shanghai Key Laboratory of Medical Imaging Computing and Computer Assisted Intervention, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
Cancer Pathog Ther. 2023 Apr 28;1(4):272-283. doi: 10.1016/j.cpt.2023.04.004. eCollection 2023 Oct.
RNA splicing alterations are widespread and play critical roles in cancer pathogenesis and therapy. Lung cancer is highly heterogeneous and causes the most cancer-related deaths worldwide. Large-scale multi-omics studies have not only characterized the mutational landscapes but also discovered a plethora of transcriptional and post-transcriptional changes in lung cancer. Such resources have greatly facilitated the development of new diagnostic markers and therapeutic options over the past two decades. Intriguingly, altered RNA splicing has emerged as an important molecular feature and therapeutic target of lung cancer. In this review, we provide a brief overview of splicing dysregulation in lung cancer and summarize the recent progress on key splicing events and splicing factors that contribute to lung cancer pathogenesis. Moreover, we describe the general strategies targeting splicing alterations in lung cancer and highlight the potential of combining splicing modulation with currently approved therapies to combat this deadly disease. This review provides new mechanistic and therapeutic insights into splicing dysregulation in cancer.
RNA剪接改变广泛存在，并在癌症发病机制和治疗中发挥关键作用。肺癌具有高度异质性，在全球范围内导致了最多的癌症相关死亡。大规模多组学研究不仅描绘了突变图谱，还发现了肺癌中大量的转录和转录后变化。在过去二十年中，这些资源极大地促进了新诊断标志物和治疗方案的开发。有趣的是，RNA剪接改变已成为肺癌的一个重要分子特征和治疗靶点。在本综述中，我们简要概述了肺癌中的剪接失调，并总结了导致肺癌发病机制的关键剪接事件和剪接因子的最新进展。此外，我们描述了针对肺癌剪接改变的一般策略，并强调了将剪接调节与目前批准的疗法相结合来对抗这种致命疾病的潜力。本综述为癌症中的剪接失调提供了新的机制和治疗见解。
