Wang Xiangyu, Yang Jianhua, Yang Wanting, Sheng Haiyang, Jia Buyun, Cheng Peng, Xu Shanshan, Hong Xinhui, Jiang Chuanwei, Yang Yinfeng, Wu Ziyin, Wang Jinghui
School of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, Anhui, China.
School of Medical Informatics Engineering, Anhui University of Chinese Medicine, Hefei, Anhui, China.
J Adv Res. 2024 Oct 28. doi: 10.1016/j.jare.2024.10.026.
The protein p53, encoded by the most frequently mutated gene TP53 in human cancers, has diverse functions in tumor suppression. As a best known transcription factor, p53 can regulate various fundamental cellular responses, ranging from the cell-cycle arrest, DNA repair, senescence to the programmed cell death (PCD), which includes autophagy, apoptosis, ferroptosis, cuproptosis, pyroptosis and disulfidoptosis. Accumulating evidence has indicated that the tumor microenvironment (TME), N-methyladenosine (mA) modification and diverse PCD are important for the progression, proliferation and metastases of cancers.
This paper aims to systematically and comprehensively summarize the multiple roles of p53 in the development of cancers from the regulation of TME, mA Modification and diverse PCD.
TME, a crucial local homeostasis environment, influences every step of tumorigenesis and metastasis. mA, the most prevalent and abundant endogenous modification in eukaryotic RNAs, plays an essential role in various biological processes, containing the progression of cancers. Additionally, PCD is an evolutionarily conserved mechanism of cell suicide and a common process in living organisms. Some forms of PCD contribute to the occurrence and development of cancer. However, the complex roles of p53 within the TME, mA modification and diverse PCD mechanisms are still not completely understood. Presently, the function roles of p53 including the wild-type and mutant p53 in different context are summarized. Additionally, the interaction between the cancer immunity, cancer cell death and RNA mA methylation and the p53 regulation during the development and progress of cancers were discussed. Moreover, the key molecular mechanisms by which p53 participates in the regulation of TME, mA and diverse PCD are also explored. All the findings will facilitate the development of novel therapeutic approaches.
蛋白质p53由人类癌症中最常发生突变的基因TP53编码，在肿瘤抑制中具有多种功能。作为最著名的转录因子，p53可以调节各种基本的细胞反应，从细胞周期停滞、DNA修复、衰老到程序性细胞死亡（PCD），其中包括自噬、凋亡、铁死亡、铜死亡、焦亡和二硫键介导的细胞死亡。越来越多的证据表明，肿瘤微环境（TME）、N-甲基腺苷（mA）修饰和多种程序性细胞死亡对于癌症的进展、增殖和转移很重要。
本文旨在从TME、mA修饰和多种程序性细胞死亡的调控方面，系统全面地总结p53在癌症发生发展中的多重作用。
TME是一个关键的局部稳态环境，影响肿瘤发生和转移的每一步。mA是真核RNA中最普遍和丰富的内源性修饰，在各种生物过程中起着重要作用，包括癌症的进展。此外，程序性细胞死亡是一种进化上保守的细胞自杀机制，是生物体内的一个常见过程。某些形式的程序性细胞死亡促进癌症的发生和发展。然而，p53在TME、mA修饰和多种程序性细胞死亡机制中的复杂作用仍未完全了解。目前，总结了p53在不同背景下包括野生型和突变型p53的功能作用。此外，还讨论了癌症免疫、癌细胞死亡与RNA mA甲基化之间的相互作用以及癌症发生发展过程中的p53调控。此外，还探讨了p53参与TME、mA和多种程序性细胞死亡调控的关键分子机制。所有这些发现将有助于开发新的治疗方法。
