Background

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), N⁶-methyladenosine (m⁶A) modification and diverse PCD are important for the progression, proliferation and metastases of cancers.

Aim of review

This paper aims to systematically and comprehensively summarize the multiple roles of p53 in the development of cancers from the regulation of TME, m⁶A Modification and diverse PCD.

Key scientific concepts of review

TME, a crucial local homeostasis environment, influences every step of tumorigenesis and metastasis. m⁶A, 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, m⁶A 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 m⁶A 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, m⁶A and diverse PCD are also explored. All the findings will facilitate the development of novel therapeutic approaches.

中文翻译：

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p53 在癌症发展中的多重作用：肿瘤微环境的调节、m6A 修饰和多种细胞死亡机制

 背景

在人类癌症中，由最常突变的基因 TP53 编码的 p53 蛋白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），包括自噬、细胞凋亡、铁死亡、铜细胞凋亡、焦亡和双硫细胞亡。越来越多的证据表明，肿瘤微环境 （TME）、N⁶-甲基腺苷 （m⁶A） 修饰和多样化的 PCD 对癌症的进展、增殖和转移很重要。

 综述目的

本文旨在从 TME 的调节、m⁶A 修饰和多样化的 PCD 系统、全面地总结 p53 在癌症发展中的多重作用。

综述的关键科学概念

TME 是一个重要的局部稳态环境，影响肿瘤发生和转移的每一步。m⁶A 是真核 RNA 中最普遍和最丰富的内源性修饰，在各种生物过程中起着至关重要的作用，遏制癌症的进展。此外，PCD 是一种进化上保守的细胞自杀机制，也是生物体中的常见过程。某些形式的 PCD 会导致癌症的发生和发展。然而，p53 在 TME 中的复杂作用、m⁶A 修饰和不同的 PCD 机制仍未完全清楚。目前，总结了 p53 在不同背景下的功能作用，包括野生型和突变型 p53。此外，还讨论了癌症发生发展过程中癌症免疫、癌细胞死亡和 RNA m⁶A 甲基化以及 p53 调节之间的相互作用。此外，还探讨了 p53 参与 TME、m⁶A 和多种 PCD 调节的关键分子机制。所有发现都将促进新型治疗方法的开发。