Yu Jingran, Sun Wei, Zhao Xiangxuan, Chen Yingying
Department of Pulmonary and Critical Care Medicine, Shengjing Hospital of China Medical University, No. 39 Huaxiang Road, Shenyang , Liaoning, 110022, China.
Department of Radiology, Shengjing Hospital of China Medical University, No. 36 Sanhao Street, Shenyang, 110004, China.
Cell Commun Signal. 2024 Dec 31;22(1):617. doi: 10.1186/s12964-024-01980-5.
Lung cancer (LC) is a highly malignant and metastatic form of cancer. The global incidence of and mortality from LC is steadily increasing; the mean 5-year overall survival (OS) rate for LC is less than 20%. This frustrating situation may be attributed to the fact that the pathogenesis of LC remains poorly understood and there is still no cure for mid to advanced LC. Methylation at the N-position of adenosine (NmA) of RNA (m(6)A) is widely present in human tissues and organs, and has been found to be necessary for cell development and maintenance of homeostasis. However, numerous basic and clinical studies have demonstrated that RNA m(6)A is deregulated in many human malignancies including LC. This can drive LC malignant characteristics such as proliferation, stemness, invasion, epithelial-mesenchymal transition (EMT), metastasis, and therapeutic resistance. Intriguingly, an increasing number of studies have also shown that eliminating RNA m(6)A dysfunction can exert significant anti-cancer effects on LC such as suppression of cell proliferation and viability, induction of cell death, and reversal of treatment insensitivity. The current review comprehensively discusses the therapeutic potential of RNA m(6)A and its underlying molecular mechanisms in LC, providing useful information for the development of novel LC treatment strategies.
肺癌(LC)是一种高度恶性且具有转移性的癌症形式。全球肺癌的发病率和死亡率正在稳步上升;肺癌的平均5年总生存率(OS)低于20%。这种令人沮丧的情况可能归因于肺癌的发病机制仍未得到充分了解,并且对于中晚期肺癌仍然没有治愈方法。RNA的N6-甲基腺苷(m6A)甲基化广泛存在于人体组织和器官中,并且已被发现对于细胞发育和体内稳态的维持是必需的。然而,大量的基础和临床研究表明,RNA m6A在包括肺癌在内的许多人类恶性肿瘤中失调。这可以驱动肺癌的恶性特征,如增殖、干性、侵袭、上皮-间质转化(EMT)、转移和治疗抗性。有趣的是,越来越多的研究还表明,消除RNA m6A功能障碍可以对肺癌产生显著的抗癌作用,如抑制细胞增殖和活力、诱导细胞死亡以及逆转治疗不敏感性。本综述全面讨论了RNA m6A在肺癌中的治疗潜力及其潜在的分子机制,为开发新的肺癌治疗策略提供了有用的信息。