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中华普外科手术学杂志(电子版)

中华普外科手术学杂志(电子版) ›› 2023, Vol. 17 ›› Issue (04) : 461 -464. doi: 10.3877/cma.j.issn.1674-3946.2023.04.028

综述

低氧微环境与实体恶性肿瘤m6A修饰的研究进展
潘玮瑄, 郝少龙, 韩威†()   
  1. 101199　北京，首都医科大学附属北京潞河医院普外科
  • 收稿日期:2023-03-31 出版日期:2023-08-26
  • 通信作者: 韩威

Research progress of hypoxic microenvironment and m6A modification in solid malignant tumors

Weixuan Pan, Shaolong Hao, Wei Han†()   

  1. Department of General Surgery, Beijing Luhe Hospital, Capital Medical University, Beijing 101100, China
  • Received:2023-03-31 Published:2023-08-26
  • Corresponding author: Wei Han
  • Supported by:
    Beijing Natural Science Foundation(7234377); Capital Health Development Research Program(2022-2-7081); Science and Technology Program of Tongzhou, Beijing(KJ2022CX016)
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潘玮瑄, 郝少龙, 韩威. 低氧微环境与实体恶性肿瘤m6A修饰的研究进展[J]. 中华普外科手术学杂志(电子版), 2023, 17(04): 461-464.

Weixuan Pan, Shaolong Hao, Wei Han. Research progress of hypoxic microenvironment and m6A modification in solid malignant tumors[J]. Chinese Journal of Operative Procedures of General Surgery(Electronic Edition), 2023, 17(04): 461-464.

低氧是实体恶性肿瘤最显著的共同病理特征之一，其在肿瘤的恶性进展中起着重要作用，是导致肿瘤治疗效果欠佳和临床预后不良的关键因素。m6A甲基化修饰可通过调节RNA的稳定性、运输、剪接和翻译等过程，影响肿瘤等多种疾病的发展恶化。许多现有研究表明，低氧微环境与m6A甲基化修饰间存在密切关联，可共同调控肿瘤的发生发展。本文综述了低氧微环境与m6A甲基化修饰在实体恶性肿瘤中的相互作用，分类阐述有关机制，旨在为探寻新的癌症指标和治疗靶点提供借鉴和理论依据。

关键词: 实体肿瘤, 低氧微环境, m6A甲基化修饰

Hypoxia is one of the most significant common pathological features of solid malignant tumors，which plays an important role in the malignant progression of tumors，and is a key factor leading to poor therapeutic effect and poor clinical prognosis. m6A methylation can affect the development and deterioration of various diseases such as tumors by regulating the stability，transport，splicing and translation of RNA. Many existing studies have shown that there is a close relationship between hypoxic microenvironment and m6A methylation modification，which can jointly regulate the occurrence and development of tumors. In this paper，the interaction between hypoxic microenvironment and m6A methylation modification in solid malignant tumors was reviewed，and the relevant mechanisms were classified to provide reference and theoretical basis for exploring new cancer indicators and therapeutic targets.

Key words: Solid Tumor, Hypoxic Microenvironment, m6A Methylation Modi?cation
表1 低氧微环境对m6A甲基化修饰的影响
m6A调节因子 肿瘤类型 低氧（HIF-1α）的调控机制 参考文献
WTAP 卵巢癌 HIF-1α促进WTAP的表达，并与DGCR8相互作用，调节miRNA-200的表达以上调HK2 [2]
METTL3/YTHDF1 肝细胞癌 抑制METTL3的表达，并使FOXO3甲基化以降低其表达水平 [3]
METTL3/METTL14 宫颈癌 DARS-AS1招募METTL3和METTL14以促进DARS翻译，HIF-1α上调METTL3和METTL14表达，促进HIF-1α/DARS-AS1/DARS /ATG5/ATG3通路表达 [4]
ALKBH5/YTHDF2 卵巢癌 上调ALKBH5以促进ITGB1的表达，增加FAK和Src蛋白的磷酸化 [6]
ALKBH5 肝细胞癌 上调ALKBH5以调节MAP3K8表达，激活ERK/JNK途径促进IL-8的表达 [7]
FTO/IGF2BP2 结直肠癌 诱导FTO降解，提高MTA1mRNA的m6A修饰水平，保持其稳定性和蛋白表达 [8]
YTHDF2 肺癌 诱导YTHDF2主要位点类泛素化，增强其与m6A修饰后mRNA的结合力 [10]
肺癌 诱导YTHDF2过表达，激活mTOR/AKT通路并调节EMT的进展 [11]
胃癌 HIF-1α诱导CBSLR/YTHDF2/CBS复合体形成，降低CBS mRNA稳定性，使ACSL4蛋白被降解 [15]
IGF2BP1 乳腺癌 HIF-1α调控lncRNA KB-1980E6.3的转录活性，与IGF2BP1结合以增加c-Myc mRNA稳定性 [14]
表2 m6A甲基化修饰对低氧微环境的影响
肿瘤生物学行为 m6A调节因子 肿瘤类型 调控机制 参考文献
代谢重编程 METTL3 肝细胞癌 HBXIP通过METTL3介导HIF-1αmRNA的m6A修饰并促进其表达 [19]
视网膜母细胞瘤 METTL3激活PI3K-Akt-mTOR信号通路与其下游代谢调节因子，促进HIF-1α表达 [21, 22]
METTL3/IGF2BP2/IGF2BP3 结直肠癌 METTL3、IGF2BP2和IGF2BP3协同保持HK2和SLC2A1 (GLUT1）mRNA的稳定性并增加其表达 [20]
FTO 肝细胞癌 FTO促进FABP5的生成，使其干扰FIH与HIF-1α的相互作用以增强HIF-1α活性，激活FABP5/HIF-1α轴 [23, 24]
转移 YTHDF2 宫颈癌 circCCDC134表达上升，在细胞核中募集p65，并作为miR-503-5p的海绵体，调节细胞质中MYB的表达，刺激HIF-1α转录 [27]
凋亡 YTHDF1 非小细胞肺癌 YTHDF1低表达以上调Keap1-Nrf2-AKR1C1依赖的抗氧化系统 [28]
免疫逃逸 WTAP/METTL3 胃癌 WTAP增加HK2 mRNA的稳定性，促进产生酸性物质，诱导H3K18乳酸化以促进METTL3表达，并导致T细胞和NK细胞选择性凋亡 [29, 30, 31]
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