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Tumor progression depends on crosstalk among the tumor microenvironment (TME), N6-methyladenosine (m6A) RNA modification, and diverse PCD pathways. The review systematically summarizes p53 functions across TME regulation, m6A-mediated control, and multiple PCD mechanisms, highlighting implications for novel therapeutic strategies.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/research-report/","Research & 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539–560  \nContents lists available at ScienceDirect  \nJournal of Advanced Research  \njournal [homepage: www. elsevier. com/locate/jare](homepage: www. elsevier. com/locate/jare)  \nMultiple roles of p53 in cancer development: Regulation of tumor microenvironment, m6A modification and diverse cell death mechanisms  \nXiangyu Wang a, Jianhua Yang b, Wanting Yang a, Haiyang Sheng c, Buyun Jia a, Peng Cheng d, Shanshan Xu Xinhui Hong a, Chuanwei Jiang a, Yinfeng Yang b, ⇑, Ziyin Wu e, ⇑, Jinghui Wang a, ⇑  \na School of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, Anhui, China b School of Medical Informatics Engineering, Anhui University of Chinese Medicine, Hefei, Anhui, China c Global Biometrics and Data Sciences, Bristol Myers Squibb, New York City, USA  \nd The First Affiliated Hospital, Anhui University of Traditional Chinese Medicine, Hefei, Anhui, China  \ne State Key Laboratory on Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Jiangsu Kanion Pharmaceutical Co. Ltd, Lianyungang, Jiangsu, China  \na  \n,  \nh i g h l i g h t s  \n Multifaceted Role of p53 in Cancer: Investigating p53’s functions in cancer biology and its impact on tumor progression and treatment.  \n Interactions in the Tumor Microenvironment: Examining p53’s role with various cell types and pathways in the TME affecting cancer.  \n p53 and m6A Modification: Exploring the link between p53 and m6A RNA modification and its implications for cancer.  \n p53 Regulation of Cell Death Mechanisms: Identifying p53’s role in autophagy, ferroptosis, and other cell death pathways.  \n Therapeutic Implications: Exploring potential targets based on p53’s roles and contributions to personalized cancer treatments.  \ng r a p h i c a l a b s t r a c t  \na r t i c l e i n f o  \nArticle history:  \nReceived 16 July 2024  \nRevised 2 October 2024  \nAccepted 23 October 2024  \nAvailable online 28 October 2024  \nKeywords: p53  \nTumor suppression  \nTumor microenvironment M6A  \na b s t r a c t  \nBackground: 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, pyroptosisand 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.  \nAim 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  \n⇑ Corresponding authors.  \nE-mail [addresses:](addresses: yinfengyang@yeah.net)[ yinfengyang@yeah.net](addresses: yinfengyang@yeah.net) (Y. Yang), [wzy1903@kanion.com](wzy1903@kanion.com) (Z. Wu), [jhwang_dlut@163.com](jhwang_dlut@163.com) (J. Wang).  \n[https://doi.org/10.1016/j.jare.2024.10.026](https://doi.org/10.1016/j.jare.2024.10.026)  \n2090-1232/© 2024 The Authors. Published by Elsevier B.V. on behalf of Cairo University.  \nThis is an open access article under the CC BY-NC-ND license ([http://creativecommons.org/licenses/by-nc-nd/4.0/](http://creativecommons.org/licenses/by-nc-nd/4.0/)).  \nX. Wang, J. Yang, W. Yang et al.  \nProgrammed cell death  \nJournal of Advanced Research 75 (2025) 539–560  \ntumorigenesis 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 suic","cbCaibb4gR4B1clZ","https://ap.wps.com/l/cbCaibb4gR4B1clZ","pdf",4393379,22,"English","# Introduction\n## The tumor microenvironment\n### Understanding the tumor microenvironment (TME)\n### The regulation of tumor microenvironment and immune response by p53\n## N6-Methyladenosine (m6A) modification\n### The key role of m6A modification in RNA biology\n### The impact of m6A modification on p53 and its role in cancer\n### Regulatory role of p53 in m6A RNA methylation","[{\"question\":\"What are the major cellular functions governed by p53 in cancer biology?\",\"answer\":\"p53 regulates cell-cycle arrest, DNA repair, senescence, and programmed cell death (PCD) pathways including autophagy, apoptosis, ferroptosis, cuproptosis, pyroptosis, and disulfidoptosis.\"},{\"question\":\"How does the tumor microenvironment (TME) interact with p53 during cancer development?\",\"answer\":\"The review describes p53 as a regulator of the TME and its immune-related responses, showing how p53 influences pathways in the microenvironment that affect cancer progression.\"},{\"question\":\"What is the relationship between p53 and m6A RNA modification?\",\"answer\":\"The paper summarizes how m6A modification connects to p53 biology, including how m6A impacts p53 and how p53 can regulate m6A RNA methylation, contributing to cancer development.\"}]","Multiple roles of p53 in cancer development: Regulation of tumor microenvironment, m6A modification and diverse cell death mechanisms | PDF",1790000393,55]